Derivatives of oxopiperidine, their production and use in therapy

FIELD: medicine.

SUBSTANCE: invention is related to new compounds that comply with formula (I) , where: n is equal to 1, Ra, Ra', Rb, Rb', identical or different, mean atom of hydrogen or alkyl or cycloalkyl group, besides, Rb and Rb' may create carbon bridge having 4 links together with hydrogen atoms of cycle, to which they are connected, R1 means cyclohexyl group, R2 means 1,2,4-triazolyl group, R3 means 1-3 groups, selected from atoms of halogen, available in any position of cycle, to which they are connected, R5 means atom of hydrogen, R4 is selected from groups of formulas (a), (b) and (c), given below, mono- or polysubstituted with aryl group: (a), (b), (c), in which: p=0, 1, 2 or 3, m=0, 1 or 2, and either a) X means link -N(R10)-, where R10 is selected from: groups -CO-NR8R9, -COOR8, -(CH2)x-OR8, -(CH2)x-COOR8, -(CH2)x-COR8, in which x=1, 2, 3 or 4, heterocycloalkyl group, condensed with aryl group, cycloalkyl, aryl, heteroaryl, alkylaryl, -CO-alkyl, -CO-cycloalkyl, -CO-heterocycloalkyl, -CO-aryl, -CO-heteroaryl, -CO-alkylaryl, -SO2-alkyl, -SO2-cycloalkyl, -SO2-aryl, besides, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups are unnecessarly substituted with one or several groups selected from atoms of halogen and groups R, R', OR, NRR', -CN, -COOR, COR; or R10 together with atom of nitrogen, to which it is connected, and with atom of carbon, available in any position of cyclic structure of formula (a), but not in neighboring position to mentioned atom of nitrogen, creates a bridge that contains 3-5 links, R8 and R9 are selected, independently from each other, from atom of hydrogen and alkyl or cycloalkyl groups; R and R' mean, independently from each other, atom of hydrogen or alkyl, cycloalkyl, aryl groups; or b) X means link - C(R6)(R7)-, where R6 is selected from the following: atom of hydrogen, atom of halogen, groups -(CH2)x-OR8, -(CH2)x-COOR8, -(CH2)x-NR8R9, -(CH2)x-CO-NR8R9 or -(CH2)x-NR8-COR9, in which x=0, 1, 2, 3 or 4, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl group, heterocycloalkyl group, condensed or non-condensed, available in spiro-position to cycle of formula (a), to which it is connected, heterocycloalkyl group, condensed with aryl group, besides, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups are unnecessarily substituted with one or several groups selected from atoms of halogen and groups R, R', OR, NRR', -CO-NRR', -CN, -COOR, OCOR, COR, NRCOOR'; and heterocycloalkyl groups are unnecessarily condensed with aryl group; R7 is selected from atoms of hydrogen and halogen and alkyl, cycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl groups, -OR, -O-aryl, -O-alkylaryl, -O-alkylheteroaryl, groups -NRR', -CO-NRR', -NR-CO-R', -NR-CO-NRR', -NR-COOR', -NO2, -CN and -COOR, R8 and R9 are selected, independently from each other, from atom of hydrogen and alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl groups, -CO-alkyl, -CO-cycloalkyl, -CO-aryl, -(CH2)x-OR, where x=0, 1, 2, 3 or 4, besides, alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl groups are unnecessarily substituted with one or several groups selected from atoms of halogen and groups R, R', OR, NRR', -CO-NRR', -CN, -COOR, OCOR, COR, NRCOOR'; or R8 and R9 create together cycloalkyl or heterocycloalkyl; R and R' mean, independently from each other, atom of hydrogen or alkyl, cycloalkyl, heterocycloalkyl, aryl, or may together create cycloalkyl or heterocycloalkyl; besides heteroaryl group represents aromatic group that contains from 5 to 10 atoms and from 1 to 4 heteroatoms, selected from nitrogen, oxygen or sulfur; heterocycloalkyl group represents cycloalkyl group, which contains from 5 to 10 atoms and contains from 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur; in the form of base or acid-additive salt, and also in the form of hydrate or solvate. Invention is also related to medicinal agent, to pharmaceutical composition, to application, to method of production, and also to compounds of formulas (IV) , (V), (VI), (XXVIII), (XXIX), (II).

EFFECT: production of new biologically active compounds, having activity of agonists of melanocortin receptors.

36 cl, 22 ex, 2 tbl

 

The invention relates to compounds which are agonists of the receptors melanocortins, to their preparation and application in therapy.

Receptors melanocortin (MC-Rs) belong to the superfamily of receptors associated with G proteins with seven transmembrane domains. Their way of transcription takes place through the production of camp (Cone, R.D., Recent Prog. Horm. Res., 1996, 51, 287,). Currently, five receptor subtypes MS-Rs: MS-R, MC2-R, MC3-R, MC4-R and MC5-R, which is expressed in various tissues, such as brain (MC, 4, 5-R), exocrine gland (MC5-R), adrenal gland (MC2-R) and leather (MS-R). Natural ligands of receptors MC-Rs - agonists are ACTH, α, β and γ-MSH, and receptor-antagonists such ligands are agouti-protein and protein-related protein agouti. No natural ligand is not highly selective in respect of any of the subtypes of the receptor, with the exception of γ-MSH, which shows some selectivity for receptor M-R.

Melanocarcinoma system is involved in numerous physiological processes, including pigmentation, inflammation, formation of food and sexual behavior (in particular, erectile function), the creation of the energy balance (regulation of body weight and the deposition of lipids), exocrine function, protection and regeneration of the nerve is s, immunomodulation, analgesia, etc.

In particular, it was shown that the receptor MS-R is involved in the development of sexual behavior (Van der Ploeg, L.H., Proc. Natl. Acad. Sci. USA, 2002, 99, 11381; Martin, W.J., Eur. J. Pharmacol., 2002, 454, 71).It has also been demonstrated in mouse models, which were intentionally deleted some receptors MC-Rs (knockout mouse)that the Central receptors MC-Rs (MC3 and 4-R) were involved in the formation of eating behavior, obesity, metabolism and the energy balance (Huszar, D., Cell, 1997, 88(1), 131; Chen, A.S., Nat. Genet., 2000, 26(1), 97; Bulter, A.A., Trends Genet., 2001, 17, S50-S54).Thus, the knockout mice showed hyperphagia and obesity. At the same time it was found that antagonists to the receptors MS and/or 4R encouraged to food intake, and, conversely, stimulation of receptors MS-R endogenous agonist, such as α-MSH, created signal saturation. These observations suggest that stimulation of the Central receptor MC-R and/or MC4-R, leading to decreased food intake and reduced body mass, is a promising approach for the treatment of obesity, which is dangerous because complicates many other diseases (hypertension, diabetes,...). Thus, the study allowed us to identify, in the first place, peptides, pseudo-peptides or cyclic peptides capable of interacting with the MS-Rs and to modulate food intake.

To save on lifespan is time effective weight loss and limit the associated susceptibility to diseases, it is necessary to develop a long-term treatment on each day. This means that the medicine appointed by therapist, should be made simple for the patient way. In this case, preferred should be the oral route of administration of drugs. However, the peptide compounds are usually not the most suitable compounds that meet this requirement.

It is therefore important to develop small molecules ones character.

From this point of view, well-known international PCT applications published under the numbers WO 02/059095, WO 02/059108, WO 03/009850 and WO 03/061660 that describe derived pieperazinove type. In other applications, such as WO 03/092690 and WO 03/0932234 described derivatives piperidino type. In applications WO 99/64002 and WO 01/70337 derivatives described type Spiro-piperidine. In the application WO 01/91752 described derivatives containing piperidine link, condensed with pyrazolinone cycle. In the application WO 02/059107 described derivatives piperidinol and pieperazinove type, substituted bicyclic structure. In applications WO 02/059117, WO 02/068388 and WO 03/009847 described derivatives piperidinol and/or pieperazinove type, substituted phenyl ring. With regard to the application WO 03/094918, it is described derivatives pieperazinove type, substituted phenyl or pyridinoline cycle. You can also call application WO 00/74679, WO 01/70708, WO 02/15909, WO 02/079146, WO 03/00949 and WO 04/024720, describe the derived type of the substituted piperidine, or an application WO 04/037797; compounds described in these patent applications, always contain aminogroup that resembles previously known peptide structure.

In addition, you can call the application WO 2005/047253, which describes compounds that are agonists of melanocortin receptors and having the General formula:

The need to constantly improve existing therapeutic agent led the inventors to the idea of developing new compounds that are agonists of receptors melanocortins.

The present invention relates to new compounds corresponding to the formula (I):

in which:

n is 1,

Ra, Ra', Rb, Rb'identical or different, denote a hydrogen atom or an alkyl or cycloalkyl group, and Rband Rb'may form together with the carbon atoms of the cycle to which they are attached, carbon bridge, containing 4-5 links

R1denotes alkyl or cycloalkyl group,

R2denotes a heteroaryl group,

R3denotes 1 to 3 groups, identical or different, are in any position of the cycle to which they are attached, selected from halogen atoms and alkyl groups, the cycle of the alkyl groups, groups or SIG, -NRR', -CO-NRR', -NR-CO-R', -NR-CO-NRR', -NR-COOR', -NO2, -CN, and-COOR,

R5denotes a hydrogen atom or an alkyl or cycloalkyl group,

R4choose from the groups of formulae (a), (b) and (C)below, optionally substituted oxopropoxy or mono - or polyamidine aryl or heteroaryl group:

in which p=0, 1, 2 or 3, m=0, 1, or 2, and either

a) X represents the group-N(R10)-, where

R10choose from:

group -(CH2)x-OR8, -(CH2)x-COOR8, -(CH2)x-NR8R9, -(CH2)x-CO-NR8R9or -(CH2)x-NR8-COR9, -(CH2)x-COR8in which x=1, 2, 3,or 4

cycloalkyl or geteroseksualnoe group condensed with aryl or heteroaryl group,

cycloalkyl, geteroseksualnoe, aryl, heteroaryl, alcylaryl, alkylchlorosilanes groups, -CO-alkyl, -CO-cycloalkyl-WITH-geteroseksualnoe, -CO-aryl, CO-heteroaryl, -CO-alcylaryl-WITH-alkylchlorosilanes groups, -CS-alkyl, -CS-cycloalkyl, -CS-geteroseksualnoe, -CS-aryl, -CS-heteroaryl, -CS-alcylaryl, -CS-alkylchlorosilanes groups, groups, CS-NR8R9, -C(=NH)-NR8R9, -SO2-alkyl, -SO2-cycloalkyl, -SO2-heterocyclyl the ilen, -SO2-aryl, -SO2-heteroaryl, -SO2-alcylaryl, -SO2-alkylchlorosilanes groups or group-SO2-NR8R9,

moreover alkyl, cycloalkyl, heterocytolysine, aryl or heteroaryl group possibly substituted by one or more groups selected from halogen atoms and the groups R, R', OR, NRR', -CO-NRR', -NRCOR', NRCONRR', -NO2, -CN, -COOR, OCOR, COR, OCONRR', NRCOOR', and

cycloalkyl or heterocytolysine group possibly condensed with aryl or heteroaryl group;

or R10together with the nitrogen atom to which it is attached and with the carbon atom located in any position of the cyclic structure of the formula (a), but not in the neighboring position to the indicated nitrogen atom, forms a bridge containing 3-5 links

R8and R9choose, independently from each other, from a hydrogen atom and alkyl, cycloalkyl, geterotsiklicheskikh, aryl, heteroaryl, alkylaryl, alkylglycerols groups, -CO-alkyl, -CO-cycloalkyl-WITH-geterotsiklicheskikh, -CO-aryl, CO-heteroaryl, -CO-alcylaryl-WITH-alkylglycerols groups, -SO2-alkyl, -SO2-cycloalkyl, -SO2-geterotsiklicheskikh, -SO2-aryl, -SO2-heteroaryl, -SO2-alcylaryl, -SO2-alkylglycerols groups, group-C(=NH)-NRR', -COOR, CO-NRR', -CS-NRR' and -(CH2)x-OR, where x=0, 1, 2, 3 or 4, and alkyl, cycloalkyl, heterocytolysine, aryl and heteroaryl groups are optionally substituted by one or more groups selected from halogen atoms and the groups R, R', OR, NRR', -CO-NRR', -NRCOR', NRCONRR', -NO2, -CN, -COOR, OCOR, COR, OCONRR', NRCOR';

or R8and R9form together cycloalkyl or heteroseksualci;

R and R represent, independently from each other, a hydrogen atom or alkyl, cycloalkyl, geterotsyklicescoe, aryl, heteroaryl, alcylaryl or alkylglycerols group, or may together form cycloalkyl or heteroseksualci;

or

b) X denotes the group-C(R6)(R7)-, where

R6choose from

hydrogen atom, halogen atom,

group -(CH2)x-OR8, -(CH2)x-COOR8, -(CH2)x-NR8R9, -(CH2)x-CO-NR8R9or -(CH2)x-NR8-COR9in which x=0, 1, 2, 3,or 4

alkyl, cycloalkyl, geteroseksualnoe, aryl, heteroaryl, alcylaryl, alkylchlorosilanes groups, -CO-alkyl, -CO-cycloalkyl-WITH-geteroseksualnoe, -CO-aryl, CO-heteroaryl, -CO-alcylaryl or-CO-alkylchlorosilanes groups, CS-alkyl, -CS-cycloalkyl, -CS-geteroseksualnoe, -CS-aryl, -CS-heteroaryl, -the S-alcylaryl, -CS-alkylchlorosilanes groups, group-CS-NR8R9, -C(=NH)-NR8R9,

cycloalkyl or geteroseksualnoe group, condensed or neskondensirovannyh in Spiro to a cycle of formula (a), to which it is attached,

cycloalkyl or geteroseksualnoe group condensed with aryl or heteroaryl group,

moreover alkyl, cycloalkyl, heterocytolysine, aryl or heteroaryl group optionally substituted by one or more groups selected from halogen atoms and the groups R, R', OR, NRR', -CO-NRR', -NRCOR', NRCONRR', -NO2, -CN, -COOR, OCOR, COR, OCONRR', NRCOR', and

cycloalkyl or heterocytolysine group optionally condensed with aryl or heteroaryl group;

R7selected from hydrogen atoms and halogen, and alkyl, cycloalkyl, aryl, heteroaryl, alcylaryl, alkylglycerols groups, -OR, -O-aryl, -O-heteroaryl, -O-alcylaryl, -O-alkylglycerols groups, group-NRR', -CO-NRR', -NR-CO-R', -NR-CO-NRR', -NR-COOR', -NO2, -CN, and-COOR,

R8and R9selected, independently from each other, from a hydrogen atom and alkyl, cycloalkyl, geterotsiklicheskikh, aryl, heteroaryl, alcylaryl, alkylglycerols groups, -CO-alkyl, -CO-cycloalkyl-WITH-geterotsiklicheskikh, -CO-aryl, -CO-hetero is rolnych, -CO-alcylaryl-WITH-alkylglycerols groups, -SO2-alkyl, -SO2-cycloalkyl, -SO2-geterotsiklicheskikh, -SO2-aryl, -SO2-heteroaryl, -SO2-alcylaryl, -SO2-alkylglycerols groups, group-C(=NH)-NRR', -COOR, -CO-NRR', -CS-NRR' and -(CH2)x-OR, where x=0, 1, 2, 3 or 4, and alkyl, cycloalkyl, heterocytolysine, aryl and heteroaryl groups are optionally substituted by one or more groups selected from halogen atoms and the groups R, R', OR, NRR', -CO-NRR', -NRCOR', NRCONRR', -NO2, -CN, -COOR, OCOR, COR, OCONRR', NRCOR';

or R8and R9form together cycloalkyl or heteroseksualci;

R and R represent, independently from each other, a hydrogen atom or alkyl, cycloalkyl, geterotsyklicescoe, aryl, heteroaryl, alcylaryl or alkylglycerols group, or together can form cycloalkyl or heteroseksualci;

in the form of a base or an acid additive salt, and also in the form of a hydrate or of MES.

Of the compounds of formula (I) according to the invention, the preferred compounds are those in which R4selected from groups of the formulas (a), (b) and (c) optionally mono - or polyamidine (di-, tri-, Tetra-substituted) aryl or heteroaryl group, in which X represents the group-C(R6)(R7)-in which

R6chosen from:

the volume of hydrogen

group -(CH2)x-OR8, -(CH2)x-COOR8, -(CH2)x-NR8R9, -(CH2)x-CO-NR8R9or -(CH2)x-NR8-COR9in which x=0, 1, 2, 3,or 4

alkyl, cycloalkyl, geteroseksualnoe, aryl, heteroaryl, alcylaryl, alkylchlorosilanes groups, -CO-alkyl, -CO-cycloalkyl-WITH-geteroseksualnoe, -CO-aryl, CO-heteroaryl, -CO-alcylaryl or-CO-alkylchlorosilanes groups,

cycloalkyl or geteroseksualnoe group Spiro-position to the cycle of the formula (a), to which it is attached,

cycloalkyl or geteroseksualnoe group condensed with aryl or heteroaryl group,

R7selected from hydrogen atoms and halogen, and alkyl, cycloalkyl, aryl, heteroaryl, alcylaryl, alkylglycerols groups, -OR, -O-aryl, -O-heteroaryl, -O-alcylaryl, -O-alkylglycerols groups, group-NRR', -CO-NRR', -NR-CO-R', -NR-CO-NRR', -NR-COOR', -NO2, -CN, and-COOR,

R8and R9selected, independently from each other, from a hydrogen atom and alkyl, cycloalkyl, geterotsiklicheskikh, aryl, heteroaryl, alcylaryl, alkylglycerols groups, -CO-alkyl, -CO-cycloalkyl-WITH-geterotsiklicheskikh, -CO-aryl, CO-heteroaryl, -CO-alkylaryl is, -CO-alkylglycerols groups, -SO2-alkyl, -SO2-cycloalkyl, -SO2-geterotsiklicheskikh, -SO2-aryl, -SO2-heteroaryl, -SO2-alcylaryl, -SO2-alkylglycerols groups, group-C(=NH)-NRR', -COOR, -CO-NRR', -CS-NRR' and -(CH2)x-OR, where x=0, 1, 2, 3,or 4

R and R represent, independently from each other, a hydrogen atom or alkyl, cycloalkyl, geterotsyklicescoe, aryl, heteroaryl, alcylaryl or alkylglycerols group.

Of the compounds of formula (I) according to the invention also prefer those in which R4selected from groups of the formulas (a), (b) and (c), in which X represents the group-C(R6)(R7)-, in which R6selected from a hydrogen atom or cycloalkyl or geteroseksualnoe group, condensed or neskondensirovannyh located in Spiro-position to the cycle of the formula (a), to which it is attached.

Preferred are those compounds in which R4selected from groups of the formulas (a), (b) and (c), in which X represents the group-C(R6)(R7)-, in which R6selected from CS-alkyl, -CS-cycloalkyl, -CS-geteroseksualnoe, -CS-aryl, -CS-heteroaryl, -CS-alcylaryl, -CS-alkylchlorosilanes groups, CS-NR8R9, -C(=NH)-NR8R9.

Preferred are those compounds in which R4 selected from groups of the formulas (a), (b) and (c), in which X represents the group-C(R6)(R7)-, in which alkyl, cycloalkyl, heterocytolysine, aryl or heteroaryl group optionally substituted by one or more groups selected from R or R', OCOR, COR, OCONRR', NRCOOR'.

Preferred are those compounds in which R4selected from groups of the formulas (a), (b) and (c), in which X represents the group-C(R6)(R7)-in which cycloalkyl or heterocytolysine optionally condensed with aryl or heteroaryl group.

Preferred are those compounds in which R4selected from groups of the formulas (a), (b) and (c), in which X represents the group-C(R6)(R7)-, in which R8and R9selected independently of one another, denote alkyl, cycloalkyl, heterocytolysine, aryl and heteroaryl groups optionally substituted by one or more groups selected from the groups R, R', OCOR, COR, OCONRR', NRCOR';

or R8and R9together form cycloalkyl or heteroseksualci.

Preferred are those compounds in which R4selected from groups of the formulas (a), (b) and (c), in which X represents the group-C(R6)(R7)-, in which R and R' may together form cycloalkyl or heteroseksualci.

Of the compounds of formula (I) according to the about the invention also prefer those in which R7is a hydrogen atom.

Of the compounds of formula (I) according to the invention also prefer those in which R4denotes a group of formula (a), where p=2, in the form as it is presented below:

Of the compounds of formula (I) according to the invention, the preferred compounds are those in which R4selected from groups of the formulas (a), (b) and (c), optionally mono - or polyamidine (di-, tri-, Tetra-substituted) aryl or heteroaryl group, in which X represents the group-N(R10)-in which

R10chosen from:

group-CO-NR8R9, -COOR8,

group -(CH2)x-OR8, -(CH2)x-COOR8, -(CH2)x-NR8R9, -(CH2)x-CO-NR8R9or -(CH2)x-NR8-COR9in which x=1, 2, 3,or 4

cycloalkyl or geteroseksualnoe group condensed with aryl or heteroaryl group,

cycloalkyl, geteroseksualnoe, aryl, heteroaryl, alcylaryl, alkylchlorosilanes group, -CO-cycloalkyl-WITH-geteroseksualnoe, -CO-heteroaryl, -CO-alcylaryl-WITH-alkylchlorosilanes group, CS-alkyl, -CS-cycloalkyl, -CS-geteroseksualnoe, -CS-aryl, -CS-heteroaryl, -CS-alcylaryl, -CS-alkylchlorosilanes groups, CSNR 8R9, -C(=NH)-NR8R9, -SO2-cycloalkyl, -SO2-geteroseksualnoe, -SO2-heteroaryl, -SO2-alcylaryl, -SO2-alkylchlorosilanes group or-SO2-NR8R9,

or R10together with the nitrogen atom to which it is attached and with the carbon atom located in any position of the cyclic structure of the formula (a), but not in the neighboring position to the nitrogen, form a bridge containing 3-5 units;

R8and R9selected, independently from each other, from a hydrogen atom and alkyl, cycloalkyl, geterotsiklicheskikh, aryl, heteroaryl, alcylaryl, alkylglycerols groups, -CO-alkyl, -CO-cycloalkyl-WITH-geterotsiklicheskikh, -CO-aryl, CO-heteroaryl, -CO-alcylaryl-WITH-alkylglycerols groups, -SO2-alkyl, -SO2-cycloalkyl, -SO2-geterotsiklicheskikh, -SO2-aryl, -SO2-heteroaryl, -SO2-alcylaryl, -SO2-alkylglycerols groups, group-C(=NH)-NRR', -COOR, -CO-NRR', -CS-NRR' and -(CH2)x-OR, where x=0, 1, 2, 3,or 4

R and R represent, independently from each other, a hydrogen atom or alkyl, cycloalkyl, geterotsyklicescoe, aryl, heteroaryl, alcylaryl or alkylglycerols group.

Prefer those compounds in which R4selected and the groups of formulae (a), (b) and (C)optionally substituted by exography, in which X represents the group-N(R10).

Prefer those compounds in which R4selected from groups of the formulas (a), (b) and (C), in which X represents the group-N(R10), in which R8and R9selected independently of one another, denote alkyl, cycloalkyl, heterocytolysine, aryl and heteroaryl groups optionally substituted by one or more groups selected from halogen atoms and the groups R, R', OR, NRR', -CO-NRR', OCOR, -NRCOR', NRCONRR', COR, -NO2, -CN, -OOR, OCONRR', NRCOR';

or R8and R9together form cycloalkyl or heteroseksualci.

Prefer those compounds in which R4selected from groups of the formulas (a), (b) and (c), in which X represents the group-N(R10), in which R10represents -(CH2)x-COR8where x=1, 2, 3, or 4.

Prefer those compounds in which R4selected from groups of the formulas (a), (b) and (C), in which X represents the group-N(R10), in which alkyl, cycloalkyl, heterocytolysine, aryl or heteroaryl group optionally substituted by one or more groups selected from R, R', OCOR, COR, OCONRR' or NRCOR'.

Prefer those compounds in which R4selected from groups of the formulas (a), (b) and (C), in which X represents the group-N(R10), in which cycloalkyl or heterocy alkylene group possibly condensed with aryl or heteroaryl group.

Also preferred are those compounds in which R4denotes a group of formula (a), where p=2, as presented below:

The compounds of formula (I) contain at least one asymmetric carbon atom. Therefore, the compounds can exist in the form of enantiomers or diastereoisomers. These enantiomers or diastereoisomers, as well as mixtures thereof, including racemic, are included in the scope of the invention.

Of the compounds of formula (I) according to the invention preferred are those compounds in which the carbon atom marked with an asterisk* in the following formula, has the configuration (R):

The compounds of formula (I) according to the invention may also exist in the form of mixtures of stereoisomers, which are included in the scope of the invention. They can also be in the form of isomers, CIS or TRANS, or isomers, endo or Exo. These isomers and their mixtures are included in the scope of the invention.

The compounds of formula (I) according to the invention can be in the form of bases or acid additive salts. Such additive salts are included in the scope of the invention.

These salts are mainly using pharmaceutically acceptable salts, but the salts of other acids that are useful, for example, for the purification or separation of compounds of formula (I), included in the scope of the invention./p>

The compounds of formula (I) according to the invention can also exist in the form of a hydrate or of a solvate, namely in the form of associations or combinations with one or more water molecules or with a solvent. Such hydrate and solvate are also included in the scope of the invention.

In the scope of the invention, if the text is not given other instructions, see below:

the halogen atom include fluorine atom, bromine or iodine;

is an alkyl group: aliphatic saturated or unsaturated group (i.e. containing 1-3 bonds of the ethylene or acetylene type)containing 1-6 carbon atoms, a linear, cyclic or branched. As example can be mentioned methyl, ethyl, sawn, ISO-propyl, boutelou, isobutylene, tert-boutelou, pentelow, neo-pentelow group, etc. and cycloalkyl group, described below, as well as alkyl groups, partially cyklinowanie, such as methyl group-cyclopropyl. Such an alkyl group may be substituted by one or more groups (for example, 1-6 groups selected from halogen atoms (education, for example, the group-CF3), and of the groups R, R', -OR, -NRR', -CO-NRR', -NRCOR', -NRCONRR', -NO2, -CN, -OOR, -OCOR, -COR, -OCONRR', -NRCOR', in which R and R represent, independently from each other, a hydrogen atom or alkyl, cycloalkyl, geterotsyklicescoe, aryl, heteroaryl, alcylaryl is whether alkylglycerols group, or may together form cycloalkyl or heteroseksualci;

- cycloalkyl group: a cyclic alkyl group containing 3-8 carbon atoms, all atoms of carbon are in a cyclic structure. As examples, group cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. Such cycloalkyl group may be substituted in the same manner as described above for alkyl groups;

- geteroseksualnoe group: cycloalkyl group, as described above, additionally containing 1-4 heteroatoms, such as nitrogen atom, oxygen and/or sulfur. This heterocytolysine group can be substituted as described above for cycloalkyl group, and may contain one or more, for example 1 or 2, ethylene or acetylanthracene connections forming, for example, 2,5-dihydro-1H-pyrrolyl;

the alkoxy group: a radical-O-alkyl in which the alkyl group has the values described above;

- aryl group, an aromatic cyclic group containing 5 to 10 parts, for example, a phenyl group. This aryl group may be substituted by one or more groups (for example, 1-6 groups selected from halogen atoms (education, for example, the group-CF3and one of the groups R, R', -OR, -NRR', -CO-NRR', -NRCOR', -NRCONRR', -NO2, -CN, -OOR, -OCOR, -COR, -OCONRR', -NRCOR'; in which R and R' denote the, independently from each other, a hydrogen atom or alkyl, cycloalkyl, geterotsyklicescoe, aryl, heteroaryl, alcylaryl or alkylglycerols group, or may together form cycloalkyl or heteroseksualci;

- alcylaryl group: alkyl group, as described above, which is itself substituted by an aryl group as described above. An example of such alcylaryl group may be benzyl;

- heteroaryl group, an aromatic cyclic group containing 5 to 10 units and containing 1-6 heteroatoms, such as nitrogen atom, oxygen and/or sulfur. As examples, a pyridinyl group. This heteroaryl group may be substituted as described for the aryl group;

- alkylchlorosilanes group: alkyl group, as defined above, which is itself substituted heteroaryl group, as defined above.

Of the compounds of formula (I) according to the invention include compounds in which n, Ra, Ra', Rb, Rb', R2, R3, R4and R5have the meanings indicated above and R1denotes cycloalkyl, such as cyclohexyl.

Of the compounds of formula (I) according to the invention can also include compounds in which n, Ra, Ra', Rb, Rb', R1, R3 , R4and R5have the meanings indicated above and R2refers to a group triazolyl (mainly, group, 1,2,4-triazolyl).

Of the compounds of formula (I) according to the invention can also include compounds in which n, Ra, Ra', Rb, Rb', R1, R2, R4and R5have the meanings indicated above and R3denotes 1 to 3 groups, identical or different, chosen from halogen atoms. Mainly, R3refers to only one group, preferably a chlorine atom.

Of the compounds of formula (I) according to the invention can also include compounds in which n, Ra, Ra', Rb, Rb', R1, R2, R3and R4have the meanings indicated above and R5denotes a hydrogen atom or an alkyl group containing 1-4 carbon atoms. Preferably, R5denotes a hydrogen atom.

You can also call other subgroups of the compounds of formula (I) according to the invention, in which R1, R2, R3, R4and R5have any of the above values, and in which:

n=1 and Ra=Ra'=Rb=Rb'=H,

n=1, Ra=Ra'=H and Rband Rb'taken together form with the carbon atoms of the cycle to which they are attached, carbon bridge, containing 4 link.

Each of the values given above for groups of Ra, Ra', R b, Rb', R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R and R'may be combined with one another to produce different subgroups of compounds of formula (I) according to the invention.

In accordance with another object of the invention relates to compounds, the names of which are given below. In the presented list of connection numbers assigned to each name, indicate the numbers of the examples of the compounds listed in the table.

5. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2-phenylethyl)piperidine-4-amine,

9. 4-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]phenol,

12.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,

13.TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,

15. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-8-methyl-8-azabicyclo[3.2.1]Octan-3-amine,

16. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine,

20. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-f is rilpivirine-4-amine,

28. 1-benzoyl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

29. 1-acetyl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

32. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1,4-dioxaspiro[4.5]Decan-8-amine,

33. N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N,N-dimethylcyclohexane-1,4-diamine,

34. 4-(aminomethyl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,

35. 3-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)-8-methyl-8-azabicyclo[3.2.1]Octan-6-ol,

36.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanol,

TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanol,

37. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(TRIFLUOROACETYL)piperidine-4-amine,

39. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)piperidine-1-carboxamide,

40.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-octoate the}amino)-1-phenylcyclohexanol,

TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-phenylcyclohexanol,

44.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-forfinal)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-forfinal)cyclohexane-1,4-diamine,

45. N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2,2,2-triptorelin,

N-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2,2,2-triptorelin,

46. N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]acetamide", she

N-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]acetamide", she

47. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(4-perbenzoic)piperidine-4-amine,

48. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(cyclopentanecarbonyl)piperidine-4-amine,

49. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(cyclobutanecarbonyl)piperid is n-4-amine,

50.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-methylcyclohexane-1,4-diamine,

52. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(pyridine-2-ylcarbonyl)piperidine-4-amine,

53. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(phenylacetyl)piperidine-4-amine,

54. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(methylsulphonyl)piperidine-4-amine,

55. N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-N-methylacetamide,

56. N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(1,3-dihydro-2H-isoindole-2-yl)cyclohexanamine,

57. N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-N-methylbenzamide,

58. ethyl-CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylate,

ethyl-TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylate,

62.TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-phenylcyclohexane-1,4-dia is h,

63.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-phenylcyclohexane-1,4-diamine,

69. N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N-methyl-N-phenylcyclohexane-1,4-diamine,

70. N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N-(4-forfinal)-N-methylcyclohexane-1,4-diamine,

73.CIS-orTRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-diethylcarbamyl,

74.CIS-orTRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-diethylcarbamyl,

75.CIS-orTRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-dimethylcyclohexylamine,

76.CIS-orTRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-dimethylcyclohexylamine,

78.CIS-N-benzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-methylcyclohexanecarboxylic,

TRANS-N-benzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-methylcyclohexanecarboxylic,

79.CIS-N -{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine,

80.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylic,

TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylic,

81.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-isonicotinohydrazide-4-amine,

82.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)cyclohexanol,

TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)cyclohexanol,

83.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(1-methyl-1Nimidazol-2-yl)carbonyl]piperidine-4-amine,

84.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(5-methylisoxazol-3-yl)carbonyl]piperidine-4-amine,

85.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-OK is Outil}-1-(3,4-differentail)piperidine-4-amine,

86. 1-[(1-tert-butyl-5-methyl-1N-pyrazole-3-yl)carbonyl]-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

87.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(3,5-dimethylisoxazol-4-yl)carbonyl]piperidine-4-amine,

88.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(3-thienylboronic]piperidine-4-amine,

89.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(pyrrolidin-1-ylcarbonyl)piperidine-4-amine,

90. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)-Nphenylpiperidine-1-carboxamide,

91. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)-N,N-dimethylpiperidin-1-carboxamid,

92. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)-N,N-diethylpiperazine-1-carboxamid,

93.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(piperidine-1-ylcarbonyl)piperidine-4-amine,

94.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(morpholine-4-ylcarbonyl)piperidine-4-amine,

95. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)- Nmethyl-Nphenylpiperidine-1-carboxamide,

96.Nbenzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)-Nmethylpiperidin-1-carboxamid,

97.N-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-methoxycyclohexanone,

98. 4-[4-(benzyloxy)phenyl]-N-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,

100. N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2-methoxyacetate,

101. 2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-2-oxoacetate,

102. 2-(benzyloxy)-N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]acetamide", she

103. 3-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it,

3-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it,

104.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(2-methoxyethyl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(2-methoxyethyl)cyclohexane-1,4-diamine,

105.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-morpholine-4-illlogical,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-morpholine-4-illlogical,

106. 1-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]pyrrolidin-2-it,

1-[TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]pyrrolidin-2-it,

107.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2 methoxyethoxy)cyclohexanamine,

108. ethyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxylate,

109. methyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxylate,

110.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2S)-piperidine-2-ylcarbonyl]piperidine-4-amine,

111.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2R)-PI is uridin-2-ylcarbonyl]piperidine-4-amine,

112.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile,

TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile,

113. 1-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperidine-2-it,

1-[TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperidine-2-it,

114. N-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]propanamide,

115.tert-boothIl (2{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-2-oxoethyl)carbamate,

116. N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]glycinamide,

117. N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]-2-hydroxyacetamido,

118. N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]-2,2-dimethylpropanamide,

N-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)PI is Eridan-1-yl]-2-oxoethyl}-amino)cyclohexyl]-2,2-dimethylpropanamide,

119.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-methoxyphenyl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-methoxyphenyl)cyclohexane-1,4-diamine,

120.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2N-tetrazol-5-yl)cyclohexanamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2N-tetrazol-5-yl)cyclohexanamine,

121. 2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}phenol,

2-{[TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}phenol,

122. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexylacetate,

123. N2-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]-N,N-dimethylglycinamide,

N2-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]-N,N-dimethylglycinamide,

124.N2-[CIS-4-({(1R)-1-(4-Harbin who yl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]glycinamide,

N2-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]glycinamide,

125. 4-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-piperazine-2-it,

4-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-piperazine-2-it,

126.CIS-4-(4-acetylpiperidine-1-yl)-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,

TRANS4-(4-acetylpiperidine-1-yl)-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,

127.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyridin-2-reparacin-4-amine,

128. methyl-N-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]glycinate,

129.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2,2-dottorati)piperidine-4-amine,

130.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-chlorophenyl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cycle is hexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}- N'(4-chlorophenyl)cyclohexane-1,4-diamine,

131. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexylphenols,

132.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-fluoro-2-were)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-fluoro-2-were)cyclohexane-1,4-diamine,

133. 4-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]amino}benzonitrile,

134. N-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]cyclopropanecarboxamide,

135.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(6-methylpyridazin-3-yl)piperidine-4-amine,

136. methyl-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]acetate

137.CIS-orTRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-(morpholine-4-ylphenyl)cyclohexane-1,4-diamine,

138.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N -(2,4-differenl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(2,4-differenl)cyclohexane-1,4-diamine,

139.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(5-herperidin-2-yl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(5-herperidin-2-yl)cyclohexane-1,4-diamine,

140.N-1N-1,2,3-benzotriazol-5-yl-N'{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-cyclohexane-1,4-diamine,

141.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyrimidine-2-reparacin-4-amine,

142. 1-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-imidazolidin-2-it,

1-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-imidazolidin-2-it,

143.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-cyclopropylidene-4-amine,

144.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-oxoethyl}-1-{[(2 S)-4,4-deformability-2-yl]carbonyl}piperidine-4-amine,

145.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4,4-diverticulectomy,

146.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(3,4-differenl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(3,4-differenl)cyclohexane-1,4-diamine,

147.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,

148.CIS-N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-Nethyl-N(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,

TRANS-N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-Nethyl-N(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,

149.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'[4-(trifluoromethyl)phenyl]cyclohexane-1,4-diamine

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'[4-(trifluoromethyl)phenyl]cyclohexane-1,4-diamine,

150.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-fluoro-3-were)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-fluoro-3-were)cyclohexane-1,4-diamine,

151.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(4,4-debtor-L-prolyl)piperidine-4-amine,

152. 1-(1Nthe benzimidazole-2-yl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

153. 1-(2,1-benzisoxazol-3-ylcarbonyl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

154. 1-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]butane-2-it,

155.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2,2,2-triptorelin)piperidine-4-amine,

156. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(4-shall ethoxyphenyl)piperidine-1-carboxamide,

157. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(4-forfinal)piperidine-1-carboxamide,

158. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(2,4-differenl)piperidine-1-carboxamide,

159. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(3,4-differenl)piperidine-1-carboxamide,

160. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(2-forfinal)piperidine-1-carboxamide,

161. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(2-methoxyphenyl)piperidine-1-carboxamide,

162. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N[4-(dimethylamino)phenyl]piperidine-1-carboxamide,

163.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(5-fluoro-1Nindol-2-yl)carbonyl]piperidine-4-amine,

164.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(pyrazin-2-ylcarbonyl]piperidine-4-amine,

165.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}--[(5-phenyl-1,3-oxazol-4-yl)carbonyl]piperidine-4-amine,

166.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(isoxazol-5-ylcarbonyl]piperidine-4-amine,

167. 3-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-6-fluoro-1,3-benzoxazol-2(3N)-he,

3-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-6-fluoro-1,3-benzoxazol-2(3N)-he,

168.N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]pyridin-2-carboxamid,

169. 2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-terfenol or

2-{[TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-terfenol,

170.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(quinoline-2-ylcarbonyl)piperidine-4-amine,

171.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(3-methylpyridin-2-yl)carbonyl]piperidine-4-amine,

172.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl-1-(1 N-1,2,4-triazole-3-ylcarbonyl)piperidine-4-amine,

173.N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]of-2.1-benzisoxazol-3-carboxamide,

174. 1-(1,3-benzothiazole-2-ylcarbonyl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

175.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(6-methylpyridin-2-yl)carbonyl]piperidine-4-amine,

176. 1-(1-benzofuran-2-ylcarbonyl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

177.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(6-herperidin-2-yl)carbonyl]piperidine-4-amine,

178.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(1-phenyl-1Npyrazole-5-yl)carbonyl]piperidine-4-amine,

179.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2,4-differentail)piperidine-4-amine,

180.CIS-N-(1,3-benzothiazol-2-ylmethyl)-N'{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-cyclohexane-1,4-diamine,

181.CIS-N-{(1R)-1(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(1,3-thiazol-2-ylmethyl)cyclohexane-1,4-diamine,

182. 2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide,

2-{[TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide,

183.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(6-vinylpyridin-2-yl)carbonyl]piperidine-4-amine,

184.TRANS-N-(tert-butyl)-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylic,

185.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(3,4-differenl)cyclohexanecarboxylic,

186.CIS-N-{(1S)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,

187.TRANS-N-{(1S)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine.

Of the preferred compounds of formula (I)in which X represents-CR6R7include the following compounds:

9. 4-[4-({(1R-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]phenol,

12.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,

13.TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,

22.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}cyclohexane-1,4-diamine,

23.TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}cyclohexane-1,4-diamine,

32.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1,4-dioxaspiro[4.5]Decan-8-amine,

33.N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N,N-dimethylcyclohexane-1,4-diamine,

34. 4-(aminomethyl)-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,

36.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanol,

TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanol,

38.N{(1R/i> )-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-phenylcyclohexanone,

40.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-phenylcyclohexanol,

TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-phenylcyclohexanol,

41.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-phenylcyclohexanecarboxylic,

TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-phenylcyclohexanecarboxylic,

44.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-forfinal)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-forfinal)cyclohexane-1,4-diamine,

45.N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2,2,2-triptorelin,

N[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2,2,2-triptorelin,

46.N[CIS--({(1 R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-acetamide", she

N[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]acetamide", she

50.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'methylcyclohexane-1,4-diamine,

55.N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-Nmethylacetamide,

56.N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(1,3-dihydro-2Nthe isoindole-2-yl)cyclohexanamine,

57.N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-Nmethylbenzamide,

58. ethyl-CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylate,

ethyl-TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylate,

59.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(trifluoromethyl)cyclohexanamine,

t the ANS-N {(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(trifluoromethyl)cyclohexanamine,

62.TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'phenylcyclohexane-1,4-diamine,

63.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'phenylcyclohexane-1,4-diamine,

64.N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2,5-dimethyl-2,5-dihydro-1N-pyrrol-1-yl)cyclohexanamine,

65.Nbenzyl-N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-Nmethylcyclohexane-1,4-diamine,

66.N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-pyrrolidin-1-illlogical,

67. 2-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}ethanol

68. 2-{benzyl[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}ethanol

69.N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-Nmethyl-Nphenylcyclohexane-1,4-diamine,

70.N'-{(1<> R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N(4-forfinal)-Nmethylcyclohexane-1,4-diamine,

71.CIS-orTRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexylcarbonyl acid,

72.CIS-orTRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexylcarbonyl acid,

73.CIS-orTRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-diethylsiloxane,

74.CIS-orTRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-diethylsiloxane,

75.CIS-orTRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-dimethylcyclohexylamine,

76.CIS-orTRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-dimethylcyclohexylamine.

Of the preferred compounds of formula (I)in which X represents-CR6R7include the following compounds:

78.CIS-N-benzil-4-({(1R)-1-(4-Harb nil)-2-[4-cyclohexyl-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-Nmethylcyclohexanecarboxylic,

TRANS-N-benzil-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-Nmethylcyclohexanecarboxylic,

79.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine,

80.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylic,

TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylic,

82.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)cyclohexanol,

TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)cyclohexanol,

97.N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-methoxycyclohexanone,

98. 4-[4-(benzyloxy)phenyl]-N{(1R)-1-(4-shall Lorenzi)-2-[4-cyclohexyl-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,

99. 4-(benzyloxy)-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,

100.N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]-2-methoxyacetate,

102. 2-(benzyloxy)-N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]acetamide", she

103. 3-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it,

3-[TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it,

104.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(2-methoxyethyl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(2-methoxyethyl)cyclohexane-1,4-diamine,

105.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-morpholine-4-illlogical,

TRANS-N-{(1R)-1-(4-chlorbenzyl)-2-4-cyclohexyl-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-morpholine-4-illlogical,

106. 1-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]pyrrolidin-2-it,

1-[TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}aminocyclohexane]pyrrolidin-2-it,

107.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2-methoxyethoxy)cyclohexanamine,

112.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}aminocyclohexanecarboxylic,

TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}aminoethoxyethanol,

113. 1-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperidine-2-it,

1-[TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperidine-2-it,

114.N[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]propanamide,

116.N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohe the power-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide,

117.N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2-hydroxyacetamido,

118.N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2,2-dimethylpropanamide,

N[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2,2-dimethylpropanamide,

119.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-methoxyphenyl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-methoxyphenyl)cyclohexane-1,4-diamine,

120.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2N-tetrazol-5-yl)cyclohexanamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2N-tetrazol-5-yl)cyclohexanamine,

121. 2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}phenol,

2-[ TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}phenol,

122. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexylacetate,

123.N2-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-N,N-dimethylglycinamide,

N2-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-N,N-dimethylglycinamide,

124.N2-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide,

N2-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide,

125. 4-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperazine-2-it,

4-[TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperazine-2-it,

126.CIS-4-(4-acetylpiperidine-1-yl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-resol-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,

TRANS4-(4-acetylpiperidine-1-yl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,

130.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-chlorophenyl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-chlorophenyl)cyclohexane-1,4-diamine,

131. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexylphenols,

132.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-2-were)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-2-were)cyclohexane-1,4-diamine,

133. 4-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}benzonitrile,

134.N[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]cyclopropanecarboxamide,

138.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(2,4-dif is arvanil)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(2,4-differenl)cyclohexane-1,4-diamine,

139.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(5-herperidin-2-yl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(5-herperidin-2-yl)cyclohexane-1,4-diamine,

140.N1H1,2,3-benzotriazol-5-yl-N'{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,

142. 1-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]imidazolidin-2-it,

1-[TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]imidazolidin-2-it,

146.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(3,4-differenl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(3,4-differenl)cyclohexane-1,4-diamine,

147.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ileti is)piperidine-1-yl]-2-oxoethyl}- N'-(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,

148.CIS-N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-Nethyl-N(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,

TRANS-N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-Nethyl-N(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,

149.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'[4-(trifluoromethyl)phenyl]cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'[4-(trifluoromethyl)phenyl]cyclohexane-1,4-diamine,

150.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-fluoro-3-were)cyclohexane-1,4-diamine,

TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(4-fluoro-3-were)cyclohexane-1,4-diamine,

167. 3-[TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)Ziklag the KSIL]-6-fluoro-1,3-benzoxazol-2(3 N)-he,

3-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-6-fluoro-1,3-benzoxazol-2(3N)-he,

168.N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]pyridin-2-carboxamid,

169. 2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-terfenol or

2-{[TRANS4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-terfenol,

173.N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]of-2.1-benzisoxazol-3-carboxamide,

180.CIS-N-(1,3-benzothiazol-2-ylmethyl)-N'{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,

181.CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'(1,3-thiazol-2-ylmethyl)cyclohexane-1,4-diamine,

182. 2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide,

2-{[TRANS4-({(1R)-1-(Chlorobenzyl)-2-[4-cyclohexyl-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide,

184.TRANS-N-(tert-boothIl)-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexanecarboxylic,

185.CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(3,4-differenl)cyclohexanecarboxylic,

186.CIS-N-{(1S)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,

187.TRANS-N-{(1S)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine.

Of the preferred compounds of formula (I)in which X represents-CR6R7include the following compounds:

101. 2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-2-oxoacetate,

115.tert-boothIl-(2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-2-oxoethyl)carbamate,

137.CIS-orTRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-(morpholine-4-ylphenyl)Ziklag is Xan-1,4-diamine,

145.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4,4-diverticulectomy.

Of the preferred compounds of formula (I)in which X represents-NR10include the following compounds:

4. 1-benzyl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

5.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2-phenylethyl)piperidine-4-amine,

6. 2-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]ethanol

7. 3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]propan-1-ol,

8. 4-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]butane-1-ol,

10.tert-boothIl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxylate,

14.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-8-azabicyclo[3.2.1]Octan-3-amine,

15.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-8-methyl-8-sabicic what about the[3.2.1]Octan-3-amine,

16.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine,

17.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}Hinkley-3-amine,

18.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}azepin-4-amine,

19.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-3-amine,

20.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-phenylpiperidine-4-amine,

21.N-{(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}piperidine-4-amine,

24. 1-benzyl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}pyrrolidin-3-amine,

28. 1-benzoyl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

29. 1-acetyl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

35. 3-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-8-methyl-8-azabicyclo[3.2.1]Octan-6-ol,

37.N-{(1 )-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(TRIFLUOROACETYL)piperidine-4-amine,

39. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxamide,

47.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(4-perbenzoic)piperidine-4-amine,

48.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(cyclopentanecarbonyl)piperidine-4-amine,

49.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(cyclobutanecarbonyl)piperidine-4-amine,

51.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(4-were)sulfonyl]piperidine-4-amine,

52.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(pyridine-2-ylcarbonyl)piperidine-4-amine,

53.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(phenylacetyl)piperidine-4-amine,

54.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(methylsulphonyl)piperidine-4-amine,

60.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-Tr the azole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-2-phenylpiperidine-4-amine,

61. (1S,3R,5S,7S)-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)adamantane-1-ol.

Of the preferred compounds of formula (I)in which X represents-NR10include the following compounds:

81.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-isonicotinohydrazide-4-amine,

83.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(1-methyl-1N-imidazol-2-yl)carbonyl]piperidine-4-amine,

84.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(5-methylisoxazol-3-yl)carbonyl]piperidine-4-amine,

85.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(3,4-differentail)piperidine-4-amine,

86. 1-[(1-tert-boothIl-5-methyl-1Npyrazole-3-yl)carbonyl]-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

87.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(3,5-dimethylisoxazol-4-yl)carbonyl]piperidine-4-amine,

88.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(3-tanika bonyl)piperidine-4-amine,

89.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(pyrrolidin-1-ylcarbonyl)piperidine-4-amine,

90. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-Nphenylpiperidine-1-carboxamide,

91. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-dimethylpiperidin-1-carboxamid,

92. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-diethylpiperazine-1-carboxamid,

93.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(piperidine-1-ylcarbonyl)piperidine-4-amine,

94.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(morpholine-4-ylcarbonyl)piperidine-4-amine,

95. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-Nmethyl-Nphenylpiperidine-1-carboxamide,

96.Nbenzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-Nmethylpiperidin-1-carboxamid,

108. ethyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-CT is oxalat,

109. methyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxylate,

110.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2S)-piperidine-2-ylcarbonyl]piperidine-4-amine,

111.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2R)-piperidine-2-ylcarbonyl]piperidine-4-amine,

127.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyridin-2-reparacin-4-amine,

128. methyl-N[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinate,

129.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2,2-dottorati)piperidine-4-amine,

135.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(6-methylpyridazin-3-yl)piperidine-4-amine,

136. methyl-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]acetate

141.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyrimidine-2-reparacin-4-amine,

143.N-{(1R)-1-(4-chlorbenzyl is)-2-[4-cyclohexyl-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-cyclopropylidene-4-amine,

144.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-{[(2S)-4,4-deformability-2-yl]carbonyl}piperidine-4-amine,

151.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(4,4-debtor-L-prolyl)piperidine-4-amine,

152. 1-(1H-benzimidazole-2-yl)-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

153. 1-(2,1-benzisoxazol-3-ylcarbonyl)-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

155.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2,2,2-triptorelin)piperidine-4-amine,

156. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(4-methoxyphenyl)piperidine-1-carboxamide,

157. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(4-forfinal)piperidine-1-carboxamide,

158. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(2,4-differenl)piperidine-1-carboxamide,

159. 4-({(1R)-1-(4-Harb nil)-2-[4-cyclohexyl-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(3,4-differenl)piperidine-1-carboxamide,

160. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(2-forfinal)piperidine-1-carboxamide,

161. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N(2-methoxyphenyl)piperidine-1-carboxamide,

162. 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N[4-(dimethylamino)phenyl]piperidine-1-carboxamide,

163.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(5-fluoro-1N-indol-2-yl)carbonyl]piperidine-4-amine,

164.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(pyrazin-2-ylcarbonyl)piperidine-4-amine,

166.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(isoxazol-5-ylcarbonyl)piperidine-4-amine,

170.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(quinoline-2-ylcarbonyl)piperidine-4-amine,

171.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(3-methylpyridin-2-yl)to rbony]piperidine-4-amine,

172.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(1N-1,2,4-triazole-3-ylcarbonyl)piperidine-4-amine,

174. 1-(1,3-benzothiazol-2-ylcarbonyl)-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

175.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(6-methylpyridin-2-yl)carbonyl]piperidine-4-amine,

176. 1-(1-benzofuran-2-ylcarbonyl)-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,

177.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(6-herperidin-2-yl)carbonyl]piperidine-4-amine,

179.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2,4-differentail)piperidine-4-amine.

Of the preferred compounds of formula (I)in which X represents-NR10include the following compounds:

154. 1-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-piperidine-1-yl]butane-2-it,

165.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(5-phenyl-1,3-oxazol-4-yl)Carbo is Il]piperidine-4-amine,

178.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(1-phenyl-1N-pyrazole-5-yl)carbonyl]piperidine-4-amine,

183.N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(6-vinylpyridin-2-yl)carbonyl]piperidine-4-amine.

In accordance with another object, the invention relates to a medicinal product, characterized in that it contains a compound of the formula (I)described above, or additive salt of this compound with a pharmaceutically acceptable acid, or a hydrate or MES the compounds of formula (I).

In accordance with another object, the invention relates to pharmaceutical compositions, characterized in that it contains a compound of the formula (I)described above, or pharmaceutically acceptable salt of this compound, or a hydrate or MES this connection, and at least one pharmaceutically acceptable excipient.

In accordance with another object, the invention relates to the use of compounds of formula (I)described above, for obtaining a medicinal product intended for the treatment and prevention of obesity, diabetes and sexual dysfunction, which can be affected by both sexes, in particular, erectile dysfunction, for the treatment of cardiovascular diseases, as well as for the applications in anti-inflammatory treatment or in the treatment of alcohol dependence.

In accordance with another object, the invention relates to a method for obtaining compounds of formula (I), characterized in that exercise rehabilitation amination of the compounds of formula (V):

in the presence of a derivative group, R4ketone type, and R1, R2, R3, R4, R5, Ra, Ra', Rb, Rb'and n have the meanings specified above.

In the present description under the protective group (KMG) to understand a group, which can, on the one hand, to protect a reactive functional group such as hydroxyl or amino group, in the synthesis process, and, on the other hand, to release the surviving reactive functional group at the end of the synthesis. Examples of protective groups, and how to protect and unprotect given in the work “Protective Groups in Organic Synthesis”, Green W. et al., 1999, 3rdEdition (John Wiley & Sons, Inc., New York).

In accordance with another object, the invention relates to compounds of formula (IV) and (V):

in which R1, Ra, Ra', Rband Rb'have the meanings specified above, Pg denotes a protective group, and

n=1, Raand Ra'identical or different, denote a hydrogen atom or an alkyl or cycloalkyl group, and Rband Rb'together with the carbon atoms qi is La, to which they are attached, form a carbon bridge, containing 4-5 links.

In accordance with another object, the invention relates to compounds of formula (VI), (XXVIII) and (XXIX), in which R1, R2, R3, R4, R5, Ra, Ra', Rb, Rb'and n have the meanings mentioned above, and in which R4denotes a group of formula (a) or (b), as described above, and Pg represents a protective group of the amine or hydroxyl functional groups:

In accordance with another object, the invention relates to compounds of the formula (II):

in which R1, Ra, Ra', Rband Rb'have the meanings specified above, Pg denotes a protective group, and

n=1, Raand Ra'identical or different, denote a hydrogen atom or an alkyl or cycloalkyl group, and Rband Rb'together with the carbon atoms of the cycle to which they are attached, form a carbon bridge, containing 4-5 links.

Under the deleted group (Lg) in the present description to understand a group, which is easily cleaved from a molecule by heterolytic rupture due simultaneously with the departure of the electron pair. Thus, this group can be easily replaced by another group, for example, during a substitution reaction. Such deleted and groups are, for example, halogen atoms or an activated hydroxyl group such as mesyl, Casilina, triftormetilfullerenov group, acetyl group, etc. are Examples of the deleted groups, as well as documents describing their getting listed in the “March''s Advanced Organic Chemistry”, J.March et al., 5thEdition, 2001, EMinter Ed.

Under Vos understand the group of tert-butoxycarbonyl, under the group Bn understand the benzyl group, under the group CBz - group benzyloxycarbonyl, under the group Fmoc - group 9-fluorenylmethoxycarbonyl, and the letter "h" means "watch".

In accordance with the invention compounds of General formula (I) can be obtained in accordance with the method presented in scheme 1.

Scheme 1:

Following the scheme 1, the compounds of formula (IV) can be obtained by reaction of a combination between the intermediate compounds of formula (II) with an amino acid of formula (III), in which the amino group protected by a protective group Pg (for example, a group of the BOC, CBz, Bn or Fmoc) in the classic combination of peptide type using as a crosslinking agent, for example, disclocated, hydrochloride 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or bromo-Tris-pyrrolidinedithiocarbamate, in the presence of hydroxybenzotriazole or without it, and using as an organic base tritium is on or diisopropylethylamine in the solvent, such as dioxane, dichloromethane or acetonitrile.

Amino acids of General formula (III) are commercially available or can be obtained according to the methods described in the literature (Williams, R., Synthesis of Optically Active α-Aminoacids, Pergamon Press, Oxford, 1989).

The compounds of formula (V) obtained by removal of the protection of the amino group in compounds of formula (IV) by methods chosen from those known to the specialist. They include, in particular, the use of triperoxonane or hydrochloric acid in dichloromethane, dioxane, tetrahydrofuran or diethyl ether, if protection was made tert-butoxycarbonyl group, or hydrogenation using a suitable metal in methanol or ethanol, if protection is carried out by groups CBz or benzyl (Bn), and the use of piperidine, if the protecting group is Fmoc, at a temperature in the range from-10C to 100C.

At the last stage of the compounds of formula (I) are obtained by the method of reductive amination carried out with compounds of the formula (V) in the presence of a derivative group, R4ketone type using a reducing agent such as sodium borohydride, triacetoxyborohydride sodium or cyanoborohydride sodium, in the presence or without acid Bronsted (such as hydrochloric acid) or Lewis acid (such as tetraisopropoxide titanium in the solvent, such as dichloroethane, dichloromethane, acetic acid or methanol, at a temperature in the range from-10C to 30C.

Derivative group, R4ketone type can be products available for sale, or they can be obtained by methods known to the expert, for example, by acylation of the free amino group or hydroxyl group in the derived ketone type, or by reductive amination of the free amino group in the derived ketone type, with itself ketone group is free or it is protected groups, such as acetylene, or in the form of hydroxyl.

In accordance with the embodiment of the last stage, depicted in scheme 1, compounds of General formula (I)in which R4correspond to the formula (a) or (b)can also be obtained through the implementation of:

stage (i): reductive amination carried out with compounds of the formula (V) in the presence of a derivative group, R4ketone type, as described above, and the group R4bear group Pg protecting the amine or hydroxyl group, then:

stage (ii): remove the protection of the amino group in the compound of formula (VI) by methods known to the expert, as described above.

In accordance with a variant, the compounds of formula (VI), which lead to compounds of formula (I)can be obtained in accordance with the tvii the way, presented in figure 2.

Scheme 2:

Following scheme 2, compounds of formula (VIII) can be obtained by the method of reductive amination, as described above, based on the amino acids of the formula (VII). The amino acid of formula (VII)in which R5=H, commercially available, or may be obtained by methods described in the literature (Williams, R., Synthesis of Optically Active α-Aminoacids, Pergamon Press, Oxford, 1989). When

R5denotes alkyl, amino acids of the formula (VII) can be obtained by alkylation of the amino acids, commercially available, which has a protected amino group, in accordance with the classical methods of alkylation, well-known specialist.

The compounds of formula (IX) can be obtained by saponification of esters of the formula (VIII), for example, in the presence of sodium hydroxide or lithium hydroxide in a solvent such as methanol, tetrahydrofuran or water, or in mixtures of these solvents.

The compounds of formula (VI) can be obtained according to the method of combination of peptide type, carried out between the intermediate compounds of formula (II) and the amino acid of formula (IX) in the classic combination of a peptide of the type described with reference to figure 1.

The compounds of formula (II) can be obtained in accordance with the method presented in scheme 3.

Scheme 3:

Following scheme 3, compounds of formula (XI) are obtained by replacing the deleted group Lg in the intermediate compounds of formula (X) on the anion heteroaryl carried out in a solvent, for example dimethylformamide, at temperatures from 20 to 200C. Then, to obtain the compounds of formula (II), removing the protective group from the amino group in compounds of formula (XI), in which Pg denotes a protective group of the amine, which is defined above with reference to figure 1, with the way that the specialist selects from among known, as described above with reference to figure 1.

If R1means tsiklogeksilnogo group, the compounds of formula (X) can be obtained by following scheme 4, representing the adaptation of the method described Sehbat et coll. (J. Med. Chem. (2002), 45, 4589).

Scheme 4:

(X) R1=cyclohexyl

In the compounds of the formula (XIIa) J denotes the hydrogen atom or alkyl. These compounds, in which Ra=Ra'=Rb=Rb'=H and n=1, is available for sale.

The compounds of formula (XIIIa) is obtained by recovery of the acids or esters of the formula (XIIa) with the use of reducing agents, such as sociallyengaged, or after the formation of the mixed anhydride in the presence of isobutylacetate and triethylamine in tetrahydrofuran or dioxane, sodium borohydride in methanol or ethanol, n and temperatures from-40C to 10S.

The compounds of formula (XIVa) is obtained by conversion of the hydroxyl group in compounds of formula (XIIIa) in the group that you want, such as mesilate or toilet, under conditions known to the expert, for example, acting methanesulfonamido or p-toluensulfonate in the presence of organic bases such as triethylamine, at temperatures from-20C to room temperature.

Then, to obtain the compounds of formula (X), hydronaut phenyl group in the compounds of formula (XIVa) in the presence of a catalyst such as Pd/C or Rh/alumina at a pressure of 5-100 bar and at a temperature in the range of 20-80 ° C, in a solvent such as methanol, ethanol or acetic acid.

The compounds of formula (XIIa), and, in General, the compounds of formula (XII)described below, in which J is a hydrogen atom or alkyl, can be obtained according to the following schemes. The compounds of formula (XII) can be divided into compounds of the various formulas (XIIb) and (XIId):

the compounds of formula (XIIb) correspond to the formula (XII)in which n=1 and Ra, Ra',

Rband Rb'identical or different, denote a hydrogen atom or an alkyl or cycloalkyl group;

the compounds of formula (XIIb) correspond to the formula (XII)in which n=1, Raand Ra'identical or different, denote a hydrogen atom or an alkyl or cycloalkyl group, and R band Rb'together with the carbon atoms of the cycle to which they are attached, form a carbon bridge, containing 4-5 units (t=1 or 2).

Methods of obtaining intermediate compounds for the synthesis piperidino type corresponding to the formula (XIIb), and tropenbos type corresponding to the formula (XIId), described in the diagrams below.

Figure 5:

Following scheme 5 piperidine formula (XIIb) can be obtained by alkylation of compounds of formula (XVb), available with halogen derivatives of groups R1(if R1is alkyl or cycloalkyl group), which is also available for sale.

Trapani formula (XIId) can be obtained according to the method depicted in scheme 7, in accordance with the data Daum et coll., described in J. Med. Chem. (1975), 18, 496.

Scheme 7:

The original complex diesters of the formula (XVIII), in which J denotes alkyl group and which are commercially available, can be restored to the compounds of formula (XIX) according to the Grignard reaction, then restore to compounds of formula (XX), for example, acting sociallyengaged or borane in a solvent such as tetrahydrofuran or diethyl ether, at temperatures from-S to room temperature.

According to a variant, when Ra=R a'=H, it is possible in one stage to go from compounds of formula (XVIII) for compounds of formula (XX), in which Ra=Ra'=H, using a reducing agent such as sociallyengaged, in a solvent such as tetrahydrofuran or diethyl ether, at temperatures from-S to room temperature.

Then the hydroxyl group of compounds of formula (XX) turn in the deleted group Lg, for example, by metilirovaniya or tiliouine, in particular, under the action of methanesulfonanilide in the presence of triethylamine at a temperature from-20C to room temperature, or using thionyl chloride at a temperature of from 20C to 120C.

The compounds of formula (XXII) can be obtained by reacting NITRILES of the formula R1-CH2CN with compounds of formula (XXI) in the presence of a base such as sodium hydride, in a solvent such as dimethylformamide, or in the presence of diisopropylamide lithium in a solvent such as tetrahydrofuran or diethyl ether, at temperatures from-C to 100C.

In accordance with a variant, it is possible to use a reagent of the formula (R1)'-CH2-CN, in which R1)' denotes the predecessor of the group R1; for example, if R1denotes cycloalkyl in the compound of formula (I), an intermediate compound for the synthesis of compounds of formula (XXII) may contain the group (R1)'= phenyl, which is th can be subjected to hydrogenation in the next stage of obtaining the desired group R 1=cycloalkyl.

Then, to obtain the compounds of formula (XIId), where J denotes a hydrogen atom, perform acid hydrolysis of the nitrile group in the compounds of formula (XII) at a temperature from 100C to 200C in solvents, such as methanol, ethanol or water. Used acids can be, for example, mineral acids such as hydrochloric acid or sulfuric acid.

The compounds of formula (XII), methods of obtaining them are described with reference to scheme 5 and 7 above, converted into the compounds of formula (X)used as starting products in scheme 3, by restoring a functional group-CO2J to the alcohol followed by the introduction of the deleted group, as described above with reference to figure 4.

According to a variant of the method presented in figure 1, when the compounds of formula (I) contain as group R4a group of formula (a), in which X=-N(R10)-, where R10is an alkyl group substituted by a hydroxyl (i.e. R10represents a group of formula -(CH2)x-OH, in which x denotes an integer from 1 to 4), an intermediate compound for the synthesis of these compounds of formula (I) may be a compound of the formula (XXVI)obtained according to scheme 8.

Scheme 8:

Following scheme 8, compound f is rmula (XXIII) can be obtained from bromodomain alcohols, in which the hydroxyl group is protected with Pg according to methods known to the expert. These methods include, in particular, the use of dihydropyran under conditions of acid catalysis in solvents such as dichloromethane.

The compounds of formula (XXV) can be obtained by substitution of bromine in compounds of formula (XXIII) on the amino group in compounds of formula (XXIV) in the presence of a mineral base such as sodium carbonate, in solvents, such as dimethylformamide or toluene, at a temperature of from 0C to 100C.

The compounds of formula (XXVI) can be obtained by oxidation of the hydroxyl group located on the circular part of the compounds of formula (XXV), for example, in the presence of oxalicacid, dimethyl sulfoxide and organic bases such as triethylamine or Diisopropylamine, or chromiferous complex, at a temperature of from-C to 60C.

Thus obtained compounds of formula (XXVI) is subjected to interaction with compounds of the formula (V) in accordance with the fact, as described with reference to figure 1 (stage reductive amination).

According to another variant of the method presented in figure 1, when the compounds of formula (I) contain as group R4a group of formula (a) of cyclohexylurea type, i.e. a group of formula (a), in which p=2 and X=-C(R6)(R7)-, where R6refers to a group-OR 8and R7and R8have the values specified above, the compounds of formula (I) can be obtained by following scheme 9.

Scheme 9:

Following scheme 9, compounds of formula (XXVIII) can be obtained by the reaction of reductive amination between the compounds of formula (XXVII), commercially available, compounds of formula (V)in circumstances which are described with reference to figure 1.

The release of the carbonyl group from the protective group in the compound of formula (XXVIII), carried out in the presence of acid, such as hydrochloric acid or pyridinylmethyl, tetrahydrofuran or acetone, yields a compound of formula (XXIX).

The compounds of formula (Ie) get the restoration of the compounds of formula (XXIX) in the conditions described with reference to figure 7.

When R8is different from a hydrogen atom, carry out the functionalization of compounds of formula (Ie), for example, alkylating in the presence of a base such as sodium hydride, a derivative group, R8that contains the deleted group Lg, and get the compounds of formula (If).

According to another variant of the method presented in figure 1, when the compounds of formula (I) contain as group R4a group of formula (a) tsiklogeksilnogo type, i.e. a group of formula (a), in which p=2 and X=-C(R6)(R7)-, where R6about the means the group-NR 8R9and R7, R8and R9have the meanings specified above, then the compounds of formula (I) can be carried out according to scheme 10.

Scheme 10:

Following scheme 10, compounds of formula (Ig) can be obtained by the reaction of reductive amination between the compounds of formula (XXIX), described with reference to figure 9, and amines of the formula R8R9NH, in the conditions described with reference to figure 1.

In schemes 1-10 of the initial compounds and the reagents, when their receipt is not described, are products that are commercially available or described in the literature or can be obtained according to the methods described in the literature or known to the expert.

The present invention relates also to compounds of formula (VI), (VIII), (IX), (XIId), (XXVIII) and (XXIX), suitable as intermediate products for the synthesis of compounds of formula (I).

Other compounds suitable as intermediate products for the synthesis of compounds of formula (I) and forming part of the invention are compounds of formula (II),(IV),(V), (X),(XI), (XIIa), (XIIb), (XIIIa) and (XIVa)in which:

n=1, Raand Ra'identical or different, denote a hydrogen atom or an alkyl or cycloalkyl, and Rband Rb'together with the carbon atoms of the cycle to which they are attached, form a carbon bridge, aderrasi 4-5 units (t=1 or 2).

The following examples describe some of the compounds according to the invention. These examples are not limiting in nature and serve only as illustration of the present invention. Rooms compounds specified in the examples are numbers that are listed in the following table, which illustrates the chemical structure and physical properties of the compounds according to the invention.

Example 1:N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine(compound No. 1)

1.1:tert-boothIl-4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate.

Dissolved in a nitrogen atmosphere 48 g of 1-(tert-boothoxycarbonyl)-4-phenylpiperidine-4-carboxylic acid, commercially available, 437 ml of anhydrous tetrahydrofuran. The medium is cooled to-20C and then add 24 ml of triethylamine followed by the introduction of 21 g of isobutylacetate. After stirring for 1 hour the precipitate is filtered off. The filtrate is cooled to-20C and administered portions of 17.8 g of sodium borohydride. The stirring is continued for 1 hour. Then added at 0C 125 ml of methanol, then 2N sulfuric acid solution. Extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is then washed with a 2N aqueous solution of sodium hydroxide. After drying over Na2SO4and evaporation doshpoluur 30,7 g tert-boothIl-4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate.

1.2:tert-boothIl-4-{[(methylsulphonyl)oxy]methyl}-4-phenylpiperidine-1-carboxylate.

Placed at 0C 2.3 gtert-boothIl-4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate in 70 ml of dichloromethane. After adding 1,68 ml of triethylamine are slowly added at 0 metalachlor. Stirred for 1 hour at room temperature and add 30 ml of aqueous saturated solution of ammonium chloride. Extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with N2Oh, then a 1%aqueous solution of sodium carbonate and again with water. After drying over MgSO4and evaporation to dryness, the crude residue absorb the ethyl acetate and n-heptane. After sedimentation get 2,72 gtert-boothIl-4-{[(methylsulphonyl)oxy]methyl}-4-phenylpiperidine-1-carboxylate.

1.3:tert-boothIl-4-cyclohexyl-4-{[(methylsulphonyl)oxy]methyl}piperidine-1-carboxylate.

The reactor was placed 15 gtert-boothIl-4-{[(methylsulphonyl)oxy]methyl}-4-phenylpiperidine-1-carboxylate in 406 ml of ethanol, then add 4,18 g of a 5%rhodium on coal. The reactor was shaken for 4 hours at 30 ° C and hydrogen pressure of 100 bar. After filtration of the catalyst on the Whatman filter and washing with dichloromethane, the filtrate concentrated and receive of 14.76 gtert-boothIl-4-cyclohexyl-4-{[(methylsulphonyl)oxy]m is Teal}piperidine-1-carboxylate.

1.4:tert-boothIl-4-cyclohexyl-4-(1N-1,2,4-triazole-1-ylmethyl)piperidine-1-carboxylate.

Introducing nitrogen atmosphere 7,83 gtert-boothIl-4-cyclohexyl-4-{[(methylsulphonyl)oxy]methyl}piperidine-1-carboxylate and of 5.68 g of 1,2,4-triazole sodium in the vessel with a capacity of 100 ml was Added 42 ml of dimethylformamide. After carrying out the reaction in a microwave oven at a power of 150 W, a temperature of 150C for 1 hour 30 minutes, Wednesday hydrolized and extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water and concentrated to dryness. After crystallization in hexane get 4.42 gtert-boothIl-4-cyclohexyl-4-(1N-1,2,4-triazole-1-ylmethyl)piperidine-1-carboxylate.

1.5: 4-cyclohexyl-4-(1N-1,2,4-triazole-1-ylmethyl)piperidine.

Put 11.2 gtert-boothIl-4-cyclohexyl-4-(1N-1,2,4-triazole-1-ylmethyl)piperidine-1-carboxylate in 80 ml of 4N hydrochloric acid in dioxane. The reaction medium is stirred for 16 hours at room temperature. After evaporation to dryness the precipitate centrifuged and washed with diethyl ether. The resulting hydrochloride is dried over P2About5under reduced pressure. Get 9,65 g of 4-cyclohexyl-4-(1N-1,2,4-triazole-1-ylmethyl)piperidine.

1.6: 9N-fluoren-9-ylmethyl-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1N-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}carb is at.

Solubilizing 2,98 g of 4-cyclohexyl-4-(1N-1,2,4-triazole-1-ylmethyl)piperidine in 100 ml of dichloromethane in the presence of 5.06 g of 4-chloro-D-Fmoc-phenylalanine, of 1.62 g of hydroxybenzotriazole, 2.3 g of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 2.3 ml of diisopropylethylamine. The mixture is stirred for 16 hours at room temperature. After evaporation to dryness the residue is washed with a saturated aqueous solution of ammonium chloride, then with water. After drying over Na2SO4and concentration to dryness, the obtained crude product chromatographic, elwira with a gradient of methanol in dichloromethane, varying from 0% to 3%. Get 7,8 g 9N-fluoren-9-ylmethyl-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1N-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}carbamate

1.7: (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine.

Solubilizing 6,98 g 9N-fluoren-9-ylmethyl-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1N-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}carbamate in 82 ml of dichloromethane, then added to 10.6 ml of piperidine. Stirred at room temperature for 16 hours under nitrogen atmosphere. After evaporation of the reaction medium obtained crude product chromatographic, elwira with a gradient of methanol/ammonium hydroxide in dichloromethane, changing from 99/1/0,1 to 90/10/1, and get 4,19 g ( R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-oxoprop-2-amine.

1.8:tert-boothIl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxylate.

Solubilizing 0.20 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-oxoprop-2-amine in 2.3 ml of dichloromethane in the presence of 0.93 gN-Vos-piperidone. Mixing support 10 minutes at 0C, then added to 0.13 g triacetoxyborohydride sodium in the atmosphere of nitrogen. The stirring is continued for 18 hours at room temperature. After hydrolysis is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with saturated aqueous sodium carbonate. After drying over MgSO4and evaporation to dryness receive 0,29 gtert-boothIl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxylate, which was used without purification in the next stage.

1.9: hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine.

Put 0.29 gramstert-boothIl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxylate in 1,17 ml of 4N chlorite is todarodes acid in dioxane. Reaction medium grind for 20 minutes at room temperature, then the precipitate centrifuged and washed with diethyl ether. The resulting hydrochloride is dried over P2About5under reduced pressure. Obtain 0.26 g of the hydrochloridetert-boothIl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine in the form of a solid white color. Tplate=S; M+N+=513, [α]D20=-2,0 (c=1,002 g/100 ml, Meon).

Example 2:N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine(compound No. 3)

Solubilizing 0.25 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-oxoprop-2-amine, obtained in stage 1.7, 2.9 ml of dichloromethane in the presence of 0.06 g of cyclohexanone. The reaction medium is cooled to 0C, then add in nitrogen atmosphere 0.16 g of triacetoxyborohydride sodium. Stirring is carried out for 18 hours at room temperature. After hydrolysis is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with saturated aqueous sodium carbonate. After drying with MgSO4and evaporation to dryness the resulting crude product chromatographic on silica gel, elwira a 9/1 mixture of dichloromethane and methanol. P is to obtain 0.25 g N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}of cyclohexanamine in a solid white color.

Tplate=60C; M+N+=512

Example 3: 2-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]ethanol(compound No. 6)

3.1: 2-(2-bromoethoxy)tetrahydro-2N-Piran.

Place of 3.97 ml bromoethanol in 44 ml of tetrahydrofuran. The solution is cooled to-10 ° C in nitrogen atmosphere. Then add the 5.51 ml of 3,4-dihydro-2NPiran and 0.20 g of p-toluensulfonate acid. The reaction medium is stirred for 16 hours at-10C. After dilution with diethyl ether, the organic phase is washed with saturated aqueous sodium bicarbonate, then with water, dried over Na2SO4and concentrate to dryness to obtain 11 g of 2-(2-bromoethoxy)tetrahydro-2N-Piran.

3.2: 1-[2-(tetrahydro-2N-Piran-2-yloxy)ethyl]piperidine-4-ol.

Dissolved in a nitrogen atmosphere of 2.72 g of 2-(2-bromoethoxy)tetrahydro-2N-Piran, 1.31 g of 4-hydroxypiperidine and of 2.33 g of potassium carbonate in 130 ml of dimethylformamide. After stirring for 16 hours type of 1.31 g of 4-hydroxypiperidine and of 2.33 g of potassium carbonate. The stirring is continued for 72 hours. After aqueous hydrolysis is extracted with dichloromethane until the depletion of the aqueous phase. Organic Gazpromviet water, dried over Na2SO4and concentrate to dryness. The resulting crude product chromatographic on silica gel, elwira with a gradient of methanol/ammonium hydroxide in dichloromethane, varying from 0% to 90/10/1, and earn 1.25 g of 1-[2-(tetrahydro-2N-Piran-2-yloxy)ethyl]piperidine-4-ol.

3.3: 1-[2-(tetrahydro-2N-Piran-2-yloxy)ethyl]piperidine-4-one.

Place of 0.68 ml oxalicacid in 15 ml of dichloromethane and the mixture is cooled to-S. Then slowly add 0,99 ml of dimethyl sulfoxide, diluted in 2 ml of dichloromethane, then 0.97 g of 1-[2-(tetrahydro-2N-Piran-2-yloxy)ethyl]piperidine-4-ol, dissolved in 5 ml dichloromethane. The reaction medium is stirred for 30 minutes. Then slowly add 2,49 ml of triethylamine, maintaining the temperature of S. Stirring is continued for 4 hours at room temperature. After hydrolysis is extracted with dichloromethane until the depletion of the aqueous phase. The organic phases are washed with 20%aqueous solution of sodium bicarbonate, dried over Na2SO4and concentrate to dryness. Get to 0.89 g of 1-[2-(tetrahydro-2N-Piran-2-yloxy)ethyl]piperidine-4-it.

3.4:N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-{2-(tetrahydro-2N-Piran-2-yloxy)ethyl]piperidine-4-amine.

Solubilizer of 0.30 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazo the-1-ylmethyl)piperidine-1-yl]-oxoprop-2-amine, obtained at the stage of 1.7, 3.5 ml of dichloromethane in the presence of 0.16 g of 1-[2-(tetrahydro-2N-Piran-2-yloxy)ethyl]piperidine-4-it and left to stir for 30 minutes at 0C, then added in a nitrogen atmosphere to 0.19 g triacetoxyborohydride sodium for 10 minutes at 0C, then stirred for 18 hours at room temperature. After hydrolysis with a saturated aqueous solution of potassium carbonate is extracted with dichloromethane until the depletion of the aqueous phase. After drying over MgSO4and evaporation to dryness the resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane, varying from 25% to 75%. Get 0,44 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[2-(tetrahydro-2N-Piran-2-yloxy)ethyl]piperidine-4-amine.

3.5: 2-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]ethanol.

Put 0.32 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[2-(tetrahydro-2N-Piran-2-yloxy)ethyl]piperidine-4-amine 1.05 ml of 4N hydrochloric acid in dioxane. The reaction medium is stirred for 18 hours at room temperature. The obtained precipitate is centrifuged and washed with diethyl ether. Received Hydra is chloride, dried over R 2About5under reduced pressure. Obtain 0.21 g of the hydrochloride of 2-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]ethanol in the form of a solid white color.

Tplate=S; M+N+=557, [α]D20=-2,4 (c=0,9905 g/100 ml, Meon).

Example 4:N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}tetrahydro-2N-Piran-4-amine(compound No. 2)

Solubilizing 0.25 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-oxoprop-2-amine, obtained in stage 1.7, 2.9 ml of dichloromethane in the presence of 0.06 g tetrahydro-4N-Piran-4-it. The reaction medium is cooled to 0C, then in an atmosphere of nitrogen was added 0.16 g of triacetoxyborohydride sodium. Stirring is maintained for 18 hours at room temperature. After hydrolysis with an aqueous solution of sodium bicarbonate extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is dried over MgSO4and evaporated to dryness. The resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane with methanol (9/1). Get 0,256N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}tetrahydro-2N-Piran-4-amine in the form of a solid white the Council.

Tplate =75S; M+N+=514, [α]D20=-1,7 (c=0,994 g/100 ml, Meon).

NMR1H (200 MHz, CDCl3): of 7.96 (s, 1H), of 7.90 (s, 1H), 7,25 (d, J=8 Hz, 2H), 7,14 (d, J=8 Hz, 2H), 4,18 is 2.10 (m, 14H), 2,05-of 0.82 (m, 19H).

Elemental analysis: Found: %C=64,14, %N=7,69, %N=13,22

Calculated: %C=64,43, %N=7,89, %N=13,42

Example 5: HydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}piperidine-4-amine(compound No. 21)

5.1: (2R,5S)-1-benzylpyrrolidine-2,5-dimethanol.

Place in a vessel in a nitrogen atmosphere 64,84 ml sociallyengaged (1N solution in diethyl ether) at a temperature of 0C. Then add to 6.6 g of diethyl-(2R,5S)-1-benzylpyrrolidine-2,5-in primary forms in 21 ml of diethyl ether. After the introduction of the reagents, the reaction medium is stirred at the boil under reflux for 1 hour. After cooling to 0C add 6.5 ml of water and stirring is continued for 1 hour at room temperature. The solution is filtered, and the precipitate washed several times with diethyl ether. The filtrate is dried over Na2SO4and concentrate to dryness to obtain 4.5 g (2R,5S)-1-benzylpyrrolidine-2,5-dimethanol.

5.2: (2R,5S)-bis(chloromethyl)-1-benzylpyrrolidine

Solubilizing 4.5 g (2R,5S)-1-benzylpyrrolidine-2,5-dimethanol in 68 ml of toluene, then added at 0C and 3.7 ml is Inishmore. After heating at 70 C for 2 hours, the medium is evaporated to dryness. The obtained solid product is triturated in toluene, centrifuged and dried over P2About5. Get 5.3g (2R,5S)-bis(chloromethyl)-1-benzylpyrrolidine.

5.3: 8-benzyl-3-phenyl-8-azabicyclo[3.2.1]Octan-3-carbonitrile.

Solubilizers 10 g (2R,5S)-bis(chloromethyl)-1-benzylpyrrolidine in 171 ml of dimethylformamide and added to 5.2 ml phenylacetonitrile. Then the portions enter 4,07 g of sodium hydride and the reaction medium is stirred for 3 hours at room temperature and for 1 hour at 100C. After cooling, the reaction medium was poured on ice. After adding water, extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride, then dried over MgSO4and concentrate to dryness. The resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane, varying from 0% to 2.5%and gain of 7.75 g of 8-benzyl-3-phenyl-8-azabicyclo[3.2.1]Octan-3-carbonitrile.

5.4: 8-benzyl-3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxylic acid.

Enter to 8.9 ml of sulfuric acid and 4,15 ml of water to of 7.75 g of 8-benzyl-3-phenyl-8-azabicyclo[3.2.1]Octan-3-carbonitrile. Heated under C for 1 hour, then the temperature was brought up to 130C. Then add 6 ml of ethanol and, at the same temperature the round is stirred for 3 hours. After cooling, the reaction mixture is poured on ice and alkalinized 2N aqueous solution of sodium hydroxide. Then extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride, then dried over MgSO4and concentrate to dryness. The aqueous phase is then treated with 100 g of resin DOWEX® 50×2. Then the resin was centrifuged and washed with water, tetrahydrofuran, then with methanol. The connection is transferred to the sediment with 2N ammonium hydroxide solution in methanol. After concentrating receive 1.5 g connection, which is endo-8-benzyl-3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxylic acid ammonium salt. The continuation of the synthesis refers to endo connection.

5.5: 3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxylic acid.

Solubilizer 1 g of 8-benzyl-3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxylic acid, 19.5 ml of methanol and added 1.86 g of formatmoney and 0.5 g 10%Pd/C (50% in N2About). Heated under reflux for 2 hours. After filtration, concentrated to dryness. Gain of 0.68 g of 3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxylic acid, which is used without purification in the subsequent syntheses.

5.6: 8-(tert-boothoxycarbonyl)-3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxylic acid.

Solub who are lysed to 0.68 g of 3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxylic acid in a mixture of 15 ml of tetrahydrofuran and cent to 8.85 ml of 1N aqueous sodium hydroxide solution. After 15 minutes of stirring 0.95 gtert-boothilikeborat. Stirring is continued for 18 hours. Then cool the reaction medium to 0C and add potassium sulfate to obtain an acidic pH, then add water. Extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride, then dried over MgSO4and concentrate to dryness. The resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane, varying from 0% to 10%, and obtain 0.32 g of 8-(tert-boothoxycarbonyl)-3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxylic acid.

5.7:tert-boothIl-3-(hydroxymethyl)-3-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate.

Placed in a nitrogen atmosphere 0.27 g of 8-(tert-boothoxycarbonyl)-3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxylic acid in 4 ml of tetrahydrofuran at 0 C and add to 1.63 ml of a 1N solution of borane NR3in THF. Stirring is carried out at room temperature for 72 hours. Then add 0.8 ml of 1N solution of borane and stirred for 5 hours. After adding methanol concentrated to dryness. Then add a mixture of ice, water and 1N aqueous solution of hydrochloric acid. Extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water, then feast upon the major aqueous solution of sodium chloride, then dried over MgSO4and concentrate to dryness. The resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane, varying from 0% to 3%, and obtain 0.11 gtert-boothIl-3-(hydroxymethyl)-3-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate.

5.8:tert-boothIl-3-{[(methylsulphonyl)oxy]methyl}-3-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate.

Placed in a nitrogen atmosphere at 0 C of 0.44 gtert-boothIl-3-(hydroxymethyl)-3-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate in 2 ml of dichloromethane. Then add 0.05 ml of methylchloride and 0.10 ml of triethylamine. Stirred at room temperature for 3 hours. Add 0,025 ml of methylchloride and 0.05 ml of triethylamine. After 2 hours of stirring ice and a saturated aqueous solution of sodium bicarbonate. Extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride, then dried over MgSO4and concentrate to dryness. Obtain 0.17 gtert-boothIl-3-{[(methylsulphonyl)oxy]methyl}-3-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate, which was used without purification in the next stage.

5.9:tert-boothIl-3-cyclohexyl-3-{[(methylsulphonyl)oxy]methyl}-8-azabicyclo[3.2.1]octane-8-carboxylate.

Placed in a reactor under high pressure, 0.17 gtert-boothIl-3-{[(methylsulphonyl)on the si]methyl}-3-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate, solubilizer in ethanol and added to 0.22 g of 5%Rh/C. the Reactor in which the hydrogen pressure is 110 bar, shaken for 6 hours. The reaction medium is filtered and concentrated to dryness. Obtain 0.14 gtert-boothIl-3-cyclohexyl-3-{[(methylsulphonyl)oxy]methyl}-8-azabicyclo[3.2.1]octane-8-carboxylate, used without purification in the subsequent syntheses.

5.10:tert-boothIl-3-cyclohexyl-3-(1N-1,2,4-triazole-1-ylmethyl)oxy]methyl}-8-azabicyclo[3.2.1]octane-8-carboxylate.

Put 0.09 gtert-boothIl-3-cyclohexyl-3-{[(methylsulphonyl)oxy]methyl}-8-azabicyclo[3.2.1]octane-8-carboxylate in 0.6 ml NMR in the presence 0,063 g of 1,2,4-triazole sodium. After performing the reaction in a microwave oven at 140 C for 20 minutes and at a power of 30 watts environment hydrolized and extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water, then saturated sodium chloride solution and concentrated to dryness. The resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane, varying from 0% to 3%. Get 0,017 gtert-boothIl-3-cyclohexyl-3-(1N-1,2,4-triazole-1-ylmethyl)8-azabicyclo[3.2.1]octane-8-carboxylate.

5.11: 3-cyclohexyl-3-(1N-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]octane.

Put 0.05 gtert-boothIl-3-cyclohexyl-3-(1N-1,2,4-triazole-1-ylmethyl)hydroxy-8-azabicyclo[3.2.1]octane-carboxylate in 0.6 ml of 4N hydrochloric acid in dioxane. The reaction medium is stirred for 5 hours at room temperature. After evaporation to dryness obtain 0.05 g of 3-cyclohexyl-3-(1N-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]octane, which is used for further synthesis without purification.

5.12: methylN[1-(tert-boothoxycarbonyl)piperidine-4-yl]-4-chloro-D-phenylalanine

Solubilizers 10 g of methyl ester of p-D-chlorophenylalanine in 248 ml of dichloromethane in the presence of 8.8 g of N-Boc-piperidone and 14.4 g of triacetoxyborohydride sodium in the atmosphere of nitrogen. Stirring is maintained for 18 hours at room temperature. After the introduction of methanol and evaporation to dryness the crude product absorb saturated aqueous sodium bicarbonate and extracted with ethyl acetate to depletion of the aqueous phase. After drying over MgSO4and concentration to dryness receive $ 15.87 with g methyl-N[1-(tert-boothoxycarbonyl)piperidine-4-yl]-4-chloro-D-phenylalanine.

5.13:N[1-(tert-boothoxycarbonyl)piperidine-4-yl]-4-chloro-D-phenylalanine.

Solubilizer to 15.8 g methyl-N[1-(tert-boothoxycarbonyl)piperidine-4-yl]-4-chloro-D-phenylalanine in 200 ml of a mixture of tetrahydrofuran/water (1/1) and add to 3.35 g of the hydrate of lithium hydroxide. Stirring is carried out for 16 hours at room temperature. Add potassium sulfate to establish a pH of 7. The precipitate centrifuged and washed the Ute diethyl ether. After drying over P2About5get 11,38 gN[1-(tert-boothoxycarbonyl)piperidine-4-yl]-4-chloro-D-phenylalanine.

5.14:tert-boothIl-4-({(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}amino)piperidine-1-carboxylate.

Solubilizing 0.05 g 3-cyclohexyl-3-(1N-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]octane, obtained at the stage 5.11, 2.4 ml of dichloromethane in the presence of 0.083 gN[1-(tert-boothoxycarbonyl)piperidine-4-yl]-4-chloro-D-phenylalanine obtained at the stage 5.13, 0,029 g of hydroxybenzotriazole, 0,041 g of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 0.09 ml of diisopropylethylamine. The mixture is stirred for 16 hours at room temperature. After evaporation to dryness the residue absorb 1N aqueous solution of sodium hydroxide and ethyl acetate. Extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic, elwira with a gradient of methanol in dichloromethane, varying from 0% to 10%. Get of 0.066 gtert-boothIl-4-({(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}amino)piperidine-1-carboxylate.

5.15:N{(1R)-1-(4-chloro shall ensil)-2-[3-cyclohexyl-3-(1 H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}piperidine-4-amine.

Place of 0.066 gtert-boothIl-4-({(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}amino)piperidine-1-carboxylate in 0.4 ml of 4N hydrochloric acid in dioxane. The reaction medium is stirred for 4 hours at room temperature. After evaporation to dryness the residue absorb 1N aqueous solution of sodium hydroxide and ethyl acetate. Extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic, elwira a mixture of dichloromethane with methanol to 97.5/2.5 a, then a mixture of dichloromethane/methanol/ammonium hydroxide 9/1/0,1. Get 0,020 gN{(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}piperidine-4-amine.

5.16: hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}piperidine-4-amine.

Put 0.02 gN{(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}piperidine-4-amine (0.4 ml dichloromethane and added to 0.74 ml 0,1N hydrochloric acid from ropanol. After evaporation to dryness the residue absorb water and the solution lyophilized. Get 0,024 g hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}piperidine-4-amine.

Tplate >270P; M+N+=540.

Example 6: the Hydrochloride of 1-benzoyl-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine(compound No. 28)

6.1: 1-benzoyl-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine.

Solubilizing 0,19 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-oxoprop-2-amine, obtained in stage 1.7, 2.3 ml of dichloromethane in the presence of 0.12 g of 1-benzoylpiperidine-4-it. Add in nitrogen atmosphere 0,22 g triacetoxyborohydride. Stirring is carried out for 18 hours at room temperature. After hydrolysis with a saturated aqueous solution of sodium bicarbonate, extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane, varying from 0% to 10%. Get 017 g of 1-benzoyl- N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine.

6.2: the Hydrochloride of 1-benzoyl-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine.

Put to 0.19 g of 1-benzoyl-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine in 2 ml of methanol and added to 2.7 ml 0,1N hydrochloric acid in isopropanol. After evaporation to dryness of the reaction medium grind, then centrifuged and the residue washed with diethyl ether. The resulting hydrochloride is dried over P2About5under reduced pressure. Obtain 0.17 g of the hydrochloride of 1-benzoyl-N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine in the form of a solid white color.

So melting >200C; M+N+=617, [α]D20=is+3.9 (c=0,331 g/100 ml, Meon).

Example 7: HydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(1,3-dihydro-2N-isoindole-2-yl)cyclohexanamine(compound No. 56)

7.1:N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1,4-dioxaspiro[4.5]Decan-8-amine.

Solubilizing 0,65g (2 R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, in 15 ml of dichloromethane in the presence of 0.3 g of acetal 1,4-cyclohexanedimethanol. Add in nitrogen atmosphere 0,63 g triacetoxyborohydride sodium. Stirring is carried out for 48 hours at room temperature. After hydrolysis with a saturated aqueous solution of sodium bicarbonate, extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane with methanol 95/5. Get 0,85 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1,4-dioxaspiro[4.5]Decan-8-amine.

7.2: 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanone.

Solubilizing 0,86 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1,4-dioxaspiro[4.5]Decan-8-amine in 25 ml of 6N aqueous hydrochloric acid and heated at 60C for 18 hours. Then add 3 ml of 12N aqueous hydrochloric acid solution and heated at 60C for the of 24 hours. After cooling the reaction medium, add 150 ml of dichloromethane and 50 ml of water. Then slowly add potassium carbonate to pH 10. Extracted with dichloromethane until the depletion of the aqueous phase. After drying over MgSO4and concentration to dryness, to obtain 0.88 g of 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanone, which is used without purification in the subsequent syntheses.

7.3:N({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(1,3-dihydro-2N-isoindole-2-yl)cyclohexanamine.

Solubilizing 0.35 g of 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanone 6.7 ml of dichloromethane in the presence of 0.09 g isoindoline. Add in nitrogen atmosphere 0,63 g triacetoxyborohydride sodium. Stirring is carried out for 18 hours at room temperature. After hydrolysis of a 1N aqueous solution of sodium hydroxide, extracted with dichloromethane until the depletion of the aqueous phase. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane with methanol 9/1. Get 0.2 gN({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(1,3-dihydro-2<> N-isoindole-2-yl)cyclohexanamine.

7.4 HydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(1,3-dihydro-2N-isoindole-2-yl)cyclohexanamine.

Place 0.2 gN({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(1,3-dihydro-2N-isoindole-2-yl)cyclohexanamine in 5 ml of methanol and add 3,18 ml of 0.1 N hydrochloric acid in isopropanol. After evaporation to dryness reaction medium was triturated in diethyl ether, and then the residue is centrifuged and washed with diethyl ether. The resulting hydrochloride is dried over P2About5under reduced pressure. Obtain 0.15 g of hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(1,3-dihydro-2N-isoindole-2-yl)cyclohexanamine in a solid white color.

Tplate=S; M+N+=629

Example 8: HydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-8-methyl-8-azabicyclo[3.2.1]Octan-3-amine(compound No. 15)

8.1:N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-8-methyl-8-azabicyclo[3.2.1]Octan-3-amine.

Solubilizer of 0.30 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1<> H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-oxoprop-2-amine, obtained in stage 1.7, 3.2 ml of dichloromethane in the presence of 0.11 g tropinona. Then add in the nitrogen atmosphere of 0.30 g of triacetoxyborohydride sodium. Stirring is carried out for 18 hours at room temperature. After hydrolysis, 0,5N aqueous solution of sodium hydroxide medium is extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/methanol/ammonium hydroxide, changing from 95/5/0 to 90/10/0,1. Get 0,145 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-8-methyl-8-azabicyclo[3.2.1]Octan-3-amine.

8.2: HydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-8-methyl-8-azabicyclo[3.2.1]Octan-3-amine.

Put 0,145 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-8-methyl-8-azabicyclo[3.2.1]Octan-3-amine in 2 ml of dichloromethane and added to 5.2 ml 0,1N hydrochloric acid in isopropanol. After evaporation to dryness of the reaction environment absorb the ethyl acetate and pound. Then allocate the I precipitate is centrifuged and washed with ethyl acetate. The resulting hydrochloride is dried over P2About5under reduced pressure. Get 0,095 g hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-8-methyl-8-azabicyclo[3.2.1]Octan-3-amine.

Tplate=S; M+N+=553

Example 9: HydrochlorideNbenzil-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-Nmethylcyclohexanecarboxylic(compound No. 78)

9.1:Nbenzyl-4-hydroxy-Nmethylcyclohexanecarboxylic.

Solubilizing 2.0 g 4-hydroxycyclohexanecarboxylate acid in 69 ml of dichloromethane in the presence to 3.58 ml of N-methylbenzylamine, 3,74 g of hydroxybenzotriazole, 5.32 g of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 4,94 ml diisopropylethylamine. The mixture is stirred for 16 hours at room temperature. After hydrolysis, add 14 ml of 1N aqueous solution of hydrochloric acid. Extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentrating to dryness the resulting crude product chromatographic, elwira with a gradient of methanol in dichloromethane, varying from 0% DL 10%. Get 3.57 gNbenzyl-4-hydroxy-Nmethylcyclohexanecarboxylic (a mixture of art is reisopera CIS and TRANS).

9.2:Nbenzyl-Nmethyl-4-oxocyclohexanecarboxylic

Solubilizing 3.57 gNbenzyl-4-hydroxy-Nmethylcyclohexanecarboxylic in 50 ml of dimethyl sulfoxide in the presence of 12,07 ml of triethylamine. Added dropwise a complex of sulfur trioxide with pyridine, dissolved in 25 ml of dimethyl sulfoxide, observing that the temperature of the reaction medium does not exceed 25C. After stirring for 2 hours at room temperature, environment hydrolized. After extraction with dichloromethane until the depletion of the aqueous phase the organic phase is washed twice 1N aqueous solution of hydrochloric acid, then water. After drying over MgSO4and concentration to dryness receive of 3.07 gNbenzyl-Nmethyl-4-oxocyclohexanecarboxylate used without purification in the subsequent syntheses.

9.3:Nbenzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-Nmethylcyclohexanecarboxylic.

Solubilizer of 0.30 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, in 7 ml of dichloromethane in the presence of 0.26 gNbenzyl-Nmethyl-4-oxocyclohexanecarboxylate obtained at the stage of 9.2. Then add in the nitrogen atmosphere of 0.30 g of triacetoxyborohydride sodium. Stirred for 18 hours at whom atoi temperature. After hydrolysis with a saturated aqueous solution of sodium carbonate medium is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/acetone/methanol/varying from 100/0/0 to 75/25/5. Get 0.36g and 0,090 gNbenzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-Nmethylcyclohexanecarboxylic in the form of stereoisomers (R,CIS) and (R,TRANS) is not installed configuration.

9.4: hydrochlorideNbenzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-Nmethylcyclohexanecarboxylic.

Put 0.36 gNbenzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-Nmethylcyclohexanecarboxylic in the form of a pure stereoisomer (R,CIS) or (R,TRANS) in 2 ml of dichloromethane and added to 5.2 ml 0,1N hydrochloric acid in isopropanol. After evaporation to dryness of the reaction environment absorb the ethyl acetate and pound. The resulting precipitate is centrifuged and washed with ethyl acetate. The resulting hydrochloride is dried over

P2About5under reduced giving the situation. Get 0,095 hydrochlorideNbenzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-Nmethylcyclohexanecarboxylic in the form of a pure stereoisomer (R,CIS) or (R,TRANS).

Tplate=160S; M+N+=663; [α]D20=+7,1 (0,3525 g/100 ml, DMSO)

Example 10: HydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine(compound No. 79)

10.1: 4-oxocyclohexanecarboxylate acid.

Solubilizer of 8.5 g of 4-oxocyclohexanecarboxylate in 68 ml of methanol and 45 ml of water. Add at 0C of 3.56 g of the hydrate of lithium hydroxide. After stirring for 4 hours, the reaction medium is acidified to pH 2 3N aqueous solution of hydrochloric acid. The methanol is evaporated, and the residue is extracted with ethyl acetate to depletion of the aqueous phase. After drying over MgSO4and concentration to dryness obtain 6.7 g of 4-oxocyclohexanecarboxylic acid.

10.2:N-{[(4-oxocyclohexyl)carbonyl]oxy}ethanamide.

Solubilizing 2.0 g 4-oxocyclohexanecarboxylic acid in 70 ml of dichloromethane in the presence of 1.15 gNhydroxyethylamide, 1,90 g of hydroxybenzotriazole and 1.95 g of diisopropylcarbodiimide. The mixture is stirred for 16 hours at room temperature. After hydrolysis, add 1 aqueous sodium hydroxide solution to establish a pH of 12. Extracted with dichloromethane until the depletion of the aqueous phase. After drying over MgSO4and concentrating to dryness the resulting crude product absorb 10 ml of ethyl acetate. Diisopropylcarbodiimide filtered, and the filtrate concentrated. Get 1,38 gN-{[(4-oxocyclohexyl)carbonyl]oxy}of tanimadigin.

10.3: 4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanone.

Solubilizing 1,38 gN-{[(4-oxocyclohexyl)carbonyl]oxy}ethanamide in 58 ml of ethanol and 22 ml of water. Add to 1.37 g of sodium acetate. The reaction medium is heated at 90 ° C for 18 hours. After cooling to room temperature, the ethanol is evaporated. Extracted with dichloromethane until the depletion of the aqueous phase. After drying over MgSO4and concentrating to dryness the resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane ranging from 0% to 2%. Obtain 0.5 g of 4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanone.

10.4:N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine.

Solubilizer of 0.30 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, in 7 ml of dichloromethane in the presence of at 0.19 g of 4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanone obtained at the stage of 10.3. Then add in the atmosphere and the PTA of 0.30 g of triacetoxyborohydride sodium. Stirred for 18 hours at room temperature. After hydrolysis with a saturated aqueous solution of sodium carbonate medium is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/acetone/methanol varying from 100/0/0 to 70/25/5. Obtain 0.26 g and 0.11 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine in the form of stereoisomers (R,CIS) and (R,TRANS) is not installed configuration.

10.5: hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine.

Place 0.25 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine in the form of a pure stereoisomer (R,CIS) or (R,TRANS) in 2 ml of methanol and add 4,32 ml 0,1N hydrochloric acid in isopropanol. After evaporation to dryness of the reaction environment absorb diethyl ether and triturated. The obtained precipitate is centrifuged and washed with diethyl ether. Received Hydra is chloride, dried over R 2About5under reduced pressure. Get 0,27 hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine, in the form of a pure stereoisomer (R,CIS) or (R,TRANS).

Tplate >200C; M+N+=598; [α]D20=+10,4 (0,5345 g/100 ml, DMSO).

Example 11: Hydrochloride 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)cyclohexanol(compound No. 82)

11.1: 4-(4-forfinal)-4-hydroxycyclohexanone

Placed at-35C 10,7 2 ml,5N n-butylate in 5 ml of anhydrous diethyl ether. Then add to 2.94 ml of 4-bromptonville, observing that the temperature did not exceed-30C. After stirring for 10 minutes at a temperature of 10C slowly add the resulting suspension to 3.0 g of 1,4-cyclohexanedione in 60 ml of tetrahydrofuran, placed at S. Stir Wednesday when-S for 1 hour. After hydrolysis with a saturated aqueous solution of ammonium chloride aqueous phase is extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira with a mixture of cyclohexane/ethyl acetate, ISM is the security from 8/2 to 6/4. Gain of 0.77 g of 4-(4-forfinal)-4-hydroxycyclohexanone.

11.2: 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)cyclohexanol.

Solubilizing 0.20 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, 4.7 ml of dichloromethane in the presence of 0,145 g of 4-(4-forfinal)-4-hydroxycyclohexanone obtained at the stage of 11.1. Then add in an atmosphere of nitrogen 0.25 g triacetoxyborohydride sodium. Stirred for 18 hours at room temperature. After hydrolysis with a saturated aqueous solution of sodium bicarbonate medium is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/acetone/methanol varying from 100/0/0 to 70/25/5. Obtain 0.10 g and 0.15 g of 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)of cyclohexanol in the form of stereoisomers (R,CIS) and (R,TRANS) is not installed configuration.

11.3: Hydrochloride 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)cyclohexanol.

Pomeshaut,10 g of 4-({(1 R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)of cyclohexanol in the form of a pure stereoisomer (R,CIS) or (R,TRANS) in 2 ml of methanol and add 4,32 ml 0,1N hydrochloric acid in isopropanol. After evaporation to dryness of the reaction environment absorb diethyl ether and triturated. The obtained precipitate is centrifuged and washed with diethyl ether. The resulting hydrochloride is dried over P2About5under reduced pressure. Obtain 0.1 g of the hydrochloride of 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)of cyclohexanol in the form of a pure stereoisomer (R,CIS) or (R,TRANS).

Tplate=150C; M+N+=625

Example 12: Hydrochloride 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-phenylpiperidine-1-carboxamide(compound No. 90)

12.1: 4-oxo-N-phenylpiperidine-1-carboxamide.

Place of 0.91 ml phenylisocyanate in 42 ml of dichloromethane. Then add 1,36 g piperidine-4-it 2,32 g of potassium carbonate. After stirring for 18 hours at room temperature the reaction environment hydrolized and extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with 1N aqueous solution of hydrochloric acid. PEFC is drying over MgSO 4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane ranging from 0% to 1%. Obtain 1.85 g of 4-oxo-N-phenylpiperidine-1-carboxamide as white solid.

12.2: 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-phenylpiperidine-1-carboxamide.

Solubilizing 0.25 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, 2.9 ml of dichloromethane in the presence of 0.13 g of 4-oxo-N-phenylpiperidine-1-carboxamide, obtained in stage 12.1. Then add in nitrogen atmosphere 0.16 g of triacetoxyborohydride sodium. Stirred for 18 hours at room temperature. Then add 0,013 g of 4-oxo-N-phenylpiperidine-1-carboxamide and 0,016 g triacetoxyborohydride sodium in the atmosphere of nitrogen. The stirring is continued for 24 hours. After hydrolysis of a 1N aqueous solution of sodium hydroxide medium is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/ethyl acetate/methanol/ammonium hydroxide, changing from 95/5/0,1/0 to 85/15/3/0,3. Obtain 0.35 g of 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-illogical-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-phenylpiperidine-1-carboxamide.

12.3: hydrochloride 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-phenylpiperidine-1-carboxamide.

Put 0.35 g of 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-phenylpiperidine-1-carboxamide in 2 ml of ethyl acetate and type of 0.32 ml of 2N hydrochloric acid in diethyl ether. After evaporation to dryness of the reaction environment absorb the ethyl acetate and pound. The resulting precipitate is centrifuged and washed with ethyl acetate. The resulting hydrochloride is dried over P2About5under reduced pressure. Obtain 0.1 g of the hydrochloride of 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-phenylpiperidine-1-carboxamide.

Tplate=S; M+N+=635; [α]D20=+11,4(0,861 g/100 ml, DMSO)

Example 13: Hydrochloride 3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it(compound No. 103)

13.1: 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)ethanol.

Solubilizing 3.12 g of 1,4-dioxaspiro[4.5]decane-8-it is in 80 ml of dichloromethane in the presence of 1.16 g atenoll is on. Then add in the nitrogen atmosphere of 6.75 g of triacetoxyborohydride sodium. Stirred for 18 hours at room temperature. After hydrolysis of 1N aqueous sodium hydroxide solution is extracted with dichloromethane until the depletion of the aqueous phase. After drying over MgSO4and concentration to dryness obtain 4.0 g of 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)ethanol, which is used without purification in the subsequent syntheses.

13.2: 3-(1,4-dioxaspiro[4.5]Dec-8-yl)-1,3-oxazolidin-2-it.

Placed in a nitrogen atmosphere at 0C 1.47 g of diphosgene in 50 ml of dichloromethane at 0C. Added dropwise 1.0 g of 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)ethanol obtained in stage 13.1 mixed with 3,59 ml of triethylamine. Stirring is carried out for 5 hours at room temperature. After evaporation to dryness the resulting crude product absorb dichloromethane. The organic phase is washed twice 1N aqueous solution of hydrochloric acid, then with water and saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane ranging from 0% to 2%. Obtain 1.19 g of 3-(1,4-dioxaspiro[4.5]Dec-8-yl)-1,3-oxazolidin-2-it.

13.3: 3-(4-oxocyclohexyl)-1,3-oxazolidin-2-it.

Solubilizing 0.75 g of 3-(1,4-dioxaspiro[4.5]Dec-8-yl)-1,3-oxazolidin-2-she 27.5 ml of 6N HCl. The reaction with the food heated at 65 degree Celsius for 5 hours. After bringing to room temperature slowly add sodium carbonate to establish a pH of 9. Extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane, varying from 0% to 10%. Obtain 0.11 g of 3-(4-oxocyclohexyl)-1,3-oxazolidin-2-it.

13.4: 3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it.

Solubilizing 0.26 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, in 6 ml of dichloromethane in the presence of 0.12 g of 3-(4-oxocyclohexyl)-1,3-oxazolidin-2-it is obtained at the stage of 13.3. Then add in nitrogen atmosphere 0.17 g triacetoxyborohydride sodium. Stirred for 18 hours at room temperature. After hydrolysis with a saturated aqueous solution of sodium bicarbonate medium is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/acetone/meta is ol, changing from 100/0/0 to 70/25/5. Obtain 0.18 g and 0.16 g of 3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it is in the form of stereoisomers (R,CIS) and (R,TRANS) is not installed configuration.

13.5: hydrochloride 3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it.

Put 0.18 g of 3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it is in the form of a pure stereoisomer (R,CIS) and (R,TRANS) in 2 ml of methanol and add 3.0 ml 0,1N hydrochloric acid in isopropanol. After evaporation to dryness of the reaction environment absorb diethyl ether and triturated. The resulting precipitate is centrifuged and washed with diethyl ether. The resulting hydrochloride is dried over P2About5under reduced pressure. Obtain 0.17 g of the hydrochloride of 3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it is in the form of a pure stereoisomer (R,CIS) or (R,TRANS)

Tplate=S; M+N+=598; [α]D20=+12,4 (0,899 g/100 ml, DMSO).

Example 14: Hydrochloride of 1-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triaz the l-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-pyrrolidin-2-it (compound No. 106)

14.1: 1-(1,4-dioxaspiro[4.5]Dec-8-yl)pyrrolidin-2-it.

Solubilizing 1.8 g of 1,4-dioxaspiro[4.5]decane-8-it in 100 ml of dichloromethane in the presence 3,02 g ethylcarboxylate 4 aminobutanoic acid. Then add in the nitrogen atmosphere of 3.54 g of triacetoxyborohydride sodium and of 6.96 ml of triethylamine. Stirred for 18 hours at room temperature. Get 1.5 g of 1-(1,4-dioxaspiro[4.5]Dec-8-yl)pyrrolidin-2-it.

14.2: 1-(4-oxocyclohexyl)pyrrolidin-2-he

Put 1.5 g of 1-(1,4-dioxaspiro[4.5]Dec-8-yl)pyrrolidin-2-it in 22 ml of 6N hydrochloric acid. The reaction medium is stirred for 18 hours at room temperature, and then hydrolyzing 1N aqueous solution of sodium hydroxide. Extracted with dichloromethane until the depletion of the aqueous phase. After drying over MgSO4and concentration to dryness obtain 0.45 g of 1-(4-oxocyclohexyl)pyrrolidin-2-it, which is used without purification in the subsequent syntheses.

14.3: 1-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-pyrrolidin-2-it.

Solubilizing 0.34 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, 8 ml dichloromethane in the presence of 0.17 g of 1-(4-oxocyclohexyl)pyrrolidin-2-it is obtained at the stage of 14.2. Then add in an atmosphere of nitrogen is 0.25 g triacetoxyborohydride sodium. Stirred for 18 hours at room temperature. After hydrolysis with a saturated aqueous solution of sodium bicarbonate medium is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/acetone/methanol varying from 100/0/0 to 70/25/5. Get 0.25 g and 0.21 g of 1-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-pyrrolidin-2-it is in the form of stereoisomers (R,CIS) or (R,TRANS) is not installed configuration.

14.4: the hydrochloride of 1-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-pyrrolidin-2-it.

Place 0.25 g of 1-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]pyrrolidin-2-it is in the form of a pure stereoisomer (R,CIS) or (R,TRANS) in 2 ml of ethyl acetate and add to 0.21 ml of 2N hydrochloric acid in diethyl ether. After evaporation to dryness of the reaction environment absorb the ethyl acetate and pound. The obtained precipitate is centrifuged and washed with ethyl acetate. The resulting hydrochloride is dried over P2About5 under reduced pressure. Obtain 0.24 g of the hydrochloride of 1-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-pyrrolidin-2-it is in the form of a pure stereoisomer (R,CIS) or (R,TRANS).

Tplate >200C; M+N+=595; [α]D20=+12,0 (of 0.901 g/100 ml, DMSO).

Example 15: HydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2-methoxyethoxy)cyclohexanamine(compound No. 107)

15.1: 8-(2-methoxyethoxy)-1,4-dioxaspiro[4.5]decane.

Placed in a nitrogen atmosphere of 1.32 g of 4-hydroxycyclohexanone in 17 ml of anhydrous dimethylformamide. Added 0.40 g of sodium hydride. The reaction medium is stirred for 1 hour at room temperature. Then add of 1.57 ml of 2-bromatologia ether. The reaction medium is stirred at room temperature for 18 hours. Then add 0.2 g of sodium hydride and 0.78 ml of 2-bromatologia ether. The reaction medium is stirred for 24 hours at room temperature. Then the reaction medium is poured on ice. Extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane, varying from 0% to 2%. what are square of 0.77 g of 8-(2-methoxyethoxy)-1,4-dioxaspiro[4.5]decane.

15.2: 4-(2-methoxyethoxy)cyclohexanone.

Place of 0.77 g of 8-(2-methoxyethoxy)-1,4-dioxaspiro[4.5]decane 11.9 ml of 6N hydrochloric acid and heated at 60C for 24 hours. Then add 4 ml of 12N hydrochloric acid and continue heating for 24 hours. The reaction medium is cooled to 0C and add sodium carbonate. Extracted the aqueous phase with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water. After drying over Na2SO4and concentrating to dryness the resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane, varying from 0% to 2%. Gain of 0.38 g of 4-(2-methoxyethoxy)cyclohexanone.

15.3:N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2-methoxyethoxy)cyclohexanamine.

Solubilizing 0.5 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, 11.6 ml of dichloromethane in the presence of 0.24 g of 4-(2-methoxyethoxy)cyclohexanone obtained at the stage of 15.2. Then added under nitrogen atmosphere and 0.37 g of triacetoxyborohydride sodium. Stirred for 18 hours at room temperature. After hydrolysis medium is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated water is astorm sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/acetone/methanol/varying from 100/0/0 to 70/25/5. Get 0,53 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2-methoxyethoxy)cyclohexanamine in the form of a mixture of stereoisomers (R,CIS) and (R,TRANS).

15.4: hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2-methoxyethoxy)cyclohexanamine.

Place of 0.53 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2-methoxyethoxy)cyclohexanamine in 2 ml of ethyl acetate and add to 0.21 ml 0,5N hydrochloric acid in diethyl ether. After evaporation to dryness of the reaction environment absorb the ethyl acetate and pound. The resulting precipitate is centrifuged and washed with ethyl acetate. The resulting hydrochloride is dried over

P2About5under reduced pressure. Gain of 0.54 g of hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2-methoxyethoxy)cyclohexanamine in the form of a mixture of stereoisomers (R,CIS) and (R,TRANS).

Tplate=S; M+N+=586

Example 16: HydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2S)-piperidine-2-ylcarbonyl]piperidine-4-amine(compound No. 110)

16.1:tert-boothIl(2S)-2-[(4-oxopiperidin-1-yl)carbonyl]piperidine-1-carboxylate.

Place of 0.68 g of piperidine-4-she's in 51 ml of dichloromethane in the presence of 1.15 g of (2S)-1-(tert-boothoxycarbonyl)piperidine-2-carboxylic acid, 0.68 g of hydroxybenzotriazole, 0.97 g of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 1.79 ml diisopropylethylamine. The mixture is stirred for 18 hours at room temperature. After evaporation to dryness and hydrolysis is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic, elwira with a gradient of methanol in dichloromethane ranging from 0% to 10%. Obtain 1.56 gtert-boothIl(2S)-2-[(4-oxopiperidin-1-yl)carbonyl]piperidine-1-carboxylate.

16.2:tert-boothIl(2S)-2-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]carbonyl}piperidine-1-carboxylate.

Solubilizing 0.3 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, in 7 ml of dichloromethane in the presence of 0.48 gtert-boothIl(2S)-2-[(4-oxop is peridin-1-yl)carbonyl]piperidine-1-carboxylate, obtained at the stage of 16.1. Then add in nitrogen atmosphere 0,22 g triacetoxyborohydride sodium. Stirred for 18 hours at room temperature. After addition of 0.3 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine and 0.47 g of triacetoxyborohydride sodium reaction medium is stirred for 24 hours. After hydrolysis with a saturated aqueous solution of sodium bicarbonate medium is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane ranging from 0% to 10%. Obtain 0.39 gtert-boothIl(2S)-2-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]carbonyl}piperidine-1-carboxylate.

16.3:N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2S)-piperidine-2-ylcarbonyl]piperidine-4-amine.

Solubilizing 0.39 gtert-boothIl(2S)-2-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]carbonyl}piperidine-1-carboxylate in 1 ml of dioxane. Added to 1.35 ml of 4N hydrochloric acid in diox is not. The reaction medium is stirred for 18 hours at room temperature. After evaporation to dryness, the residue absorb dichloromethane. Add saturated aqueous solution of sodium bicarbonate. Extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic, elwira a mixture of dichloromethane/methanol/ammonium hydroxide, changing from 100/0/0 to 90/10/1. Get 0,30 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2S)-piperidine-2-ylcarbonyl]piperidine-4-amine.

16.4: hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2S)-piperidine-2-ylcarbonyl]piperidine-4-amine.

Placed 0.3 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2S)-piperidine-2-ylcarbonyl]piperidine-4-amine in 2 ml of dichloromethane and added dropwise 2.4 ml 0,2N hydrochloric acid in diethyl ether. After evaporation to dryness of the reaction environment absorb diethyl ether and triturated. The resulting precipitate is centrifuged and washed with diethyl ether. The resulting hydrochloride is dried over P2About5under reduced pressure. Get 0,23 g is hydrochloride N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2S)-piperidine-2-ylcarbonyl]piperidine-4-amine.

Tplate=S; M+N+=627; [α]D20=+4,9 (0,921 g/100 ml, DMSO).

Example 17: Hydrochloride 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile(compound No. 112)

17.1: 4-[(trimethylsilyl)oxy]cyclohex-3-EN-1-carbonitrile.

Solubilizing 14.2 g of 2-(trimethylsiloxy)-1,3-butadiene and 5.3 g of Acrylonitrile in 35 ml of anhydrous toluene. Added 0.11 g of hydroquinone and the reaction medium is heated at 140 C for 24 hours. After evaporation to dryness obtain 4.0 g of 4-[(trimethylsilyl)oxy]cyclohex-3-EN-1-carbonitrile used without purification in the subsequent syntheses.

17.2: 4-oxocyclohexanecarboxylic.

Placed 4.0 g of 4-[(trimethylsilyl)oxy]cyclohex-3-EN-1-carbonitrile in 7 ml of 2%aqueous solution of sulfuric acid. After stirring for 30 minutes the reaction environment hydrolyzing saturated aqueous ammonium chloride. Extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness obtain 2.6 g of 4-oxocyclohexanecarboxylate used without further purification Sint shall see.

17.3: 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile.

Solubilizing 1,08 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, 25 ml of dichloromethane in the presence of 0.615 g of 4-oxocyclohexanecarboxylate obtained at the stage of 17.2. Then add in nitrogen atmosphere 1,32 g triacetoxyborohydride sodium. Mixing support 18 hours at room temperature. After hydrolysis with a saturated aqueous solution of sodium bicarbonate medium is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/acetone/methanol varying from 100/0/0 to 70/25/5. Obtain 0.55 g and 0.25 g of 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile, in the form of stereoisomers (R,CIS) and (R,TRANS) not established structure.

17.4: hydrochloride 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile.

Place 0.2 g of 4-({(1i> R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile in the form of a pure stereoisomer (R,CIS) or (R,TRANS) in 2 ml of dichloromethane and added to 1.86 ml 0,2N hydrochloric acid in diethyl ether. After evaporation to dryness of the reaction environment absorb diethyl ether and triturated. The resulting precipitate is centrifuged and washed with diethyl ether. The resulting hydrochloride is dried over P2About5under reduced pressure. Obtain 0.21 g of the hydrochloride of 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile in the form of a pure stereoisomer (R,CIS) or (R,TRANS).

Tplate=S; M+N+=540; [α]D20=+6,4 (C=0.8 g/100 ml, DMSO).

Example 18: HydrochlorideN[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide(compound No. 116)

18.1: methylN{CIS-4-[(tert-butoxycarbonyl)amino]cyclohexyl}-4-chloro-D-phenylalanine.

Place 10 g of the hydrochloride of methyl 4-chloro-L-phenylalanine in the presence of 8.5 g of tert-butyl(4-oxocyclohexyl)carbamate in 200 ml of dichloromethane. Add 11,0 g triacetoxyborohydride sodium. Stirring at room temperature is carried out for 18 hours. actor hydrolyzing saturated aqueous sodium bicarbonate and extracted with dichloromethane until the depletion of the aqueous phase. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/ethyl acetate/methanol/ammonium hydroxide, changing from 95/5/1/0,1 to 85/15/3/0,3. Gain of 6.1 g of methylN{CIS-4-[(tert-boothoxycarbonyl)amino]cyclohexyl}-4-chloro-D-phenylalanine and 7.4 g of methylN{TRANS-4-[(tert-boothoxycarbonyl)amino]cyclohexyl}-4-chloro-D-phenylalanine.

18.2:N{CIS-4-[(tert-butoxycarbonyl)amino]cyclohexyl}-4-chloro-D-phenylalanine.

Put 4.8 g of methylN{CIS-4-[(tert-boothoxycarbonyl)amino]cyclohexyl}-4-chloro-D-phenylalanine in 180 ml of a mixture of N2O/THF/Meon, then add 0,83 g of the hydrate of lithium hydroxide at 0C. The support mixing at room temperature for 18 hours. After evaporation of methanol and tetrahydrofuran reaction medium lyophilized. Obtain 4.5 g of limitabilityN{CIS-4-[(tert-butoxycarbonyl)amino]cyclohexyl}-4-chloro-D-phenylalanine.

18.3:tert-boothIl-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]carbamate.

Place of 2.0 g of 4-cyclohexyl-4-(1N-1,2,4-triazole-1-ylmethyl)piperidine obtained in stage 1.5 in 40 ml of dichloromethane in the presence of 3.2 g of limitabilityN{CIS-4-[(tert-butoxide the Nile)amino]cyclohexyl}-4-chloro-D-phenylalanine, obtained at the stage 18.2, 1.1 g of hydroxybenzotriazole, 1.5 g of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide and 1,68 ml diisopropylethylamine. The mixture is stirred for 16 hours at room temperature. After evaporation to dryness and hydrolysis is extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with 1N aqueous solution of hydrochloric acid, then 1N aqueous solution of sodium hydroxide and water. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic, elwira with a gradient of methanol in dichloromethane, varying from 0% to 5%. Obtain 2.4 gtert-boothIl-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]carbamate.

18.4:CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine.

Put 2.4 gtert-boothIl-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]carbamate in 5 ml of dioxane. Then add 9.6 ml of 4N hydrochloric acid in dioxane. The reaction mixture is stirred 18 hours at room temperature. After evaporation to dryness the residue absorb saturated aqueous solution of sodium bicarbonate and etelaat the om. Extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness obtain 1.98 gCIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl} cyclohexane-1,4-diamine.

18.5:tert-boothIl-(2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-2-oxoethyl)carbamate.

Put 0.7 gCIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine obtained in stage 18.4, in 40 ml of dichloromethane in the presence of 0.23 g of BOC-Gly-OH, 0.18 g of hydroxybenzotriazole, 0.25 g of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 0.24 ml of diisopropylethylamine. The mixture is stirred for 18 hours at room temperature. After evaporation to dryness and hydrolysis, extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic, elwira with a gradient of methanol in dichloromethane, varying from 0% to 10%. Obtain 0.75 gtert-boothIl-(2-{[CIS-4-({(1R)-1-(4-Harbin who yl)-2-[4-cyclohexyl-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-2-oxoethyl)carbamate.

18.6:N[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide.

Solubilizing 0.45 gtert-boothIl-(2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-2-oxoethyl)carbamate in 1 ml of dioxane. Add to 1.63 ml of 4N hydrochloric acid in dioxane, then about 1 ml of methanol. The reaction medium is stirred for 18 hours at room temperature. After evaporation to dryness the residue absorb dichloromethane. Add saturated aqueous solution of sodium bicarbonate. Extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/methanol/ammonium hydroxide, changing from 100/0/0 to 90/10/1. Obtain 0.35 gN[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide.

18.7: hydrochlorideN[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ilma who yl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide.

Put 0.35 gN[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide in 2 ml of dichloromethane and add 3.0 ml of 0,2N hydrochloric acid in diethyl ether. After evaporation to dryness of the reaction environment absorb diethyl ether and triturated. The residue is centrifuged and washed with diethyl ether. The resulting hydrochloride is dried over P2About5under reduced pressure. Obtain 0.3 g of hydrochlorideN[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide.

Tplate=S; M+N+=584; [α]D20=+0,7(0,938 g/100 ml, DMSO)

Example 19: HydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2,3-dihydro-1N-tetrazol-5-yl)cyclohexanamine(compound No. 120)

19.1:N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2,3-dihydro-1N-tetrazol-5-yl)cyclohexanamine.

Place of 0.3 g of 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile in the form of a pure isomer (R,CIS) or (R,TRANS), obtained at the stage 17.3 in 3 ml of dimethylformamide in outstay of 0.43 g of sodium azide and 0.36 ml of ammonium chloride in a sealed tube. After carrying out the reaction in a microwave oven at 140 C for 3 hours dimethylformamide is evaporated and absorb the crude residue with methanol. After filtration, the filtrate is concentrated to dryness and chromatographic on the filter C18, elwira a mixture of water/acetonitrile, gradient from 80/20 to 100/0. Get 0,13 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2,3-dihydro-1N-tetrazol-5-yl)cyclohexanamine in the form of a pure isomer (R,CIS) or (R,TRANS).

19.2: hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2,3-dihydro-1N-tetrazol-5-yl)cyclohexanamine.

Place 0.2 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2,3-dihydro-1N-tetrazol-5-yl)cyclohexanamine in the form of a pure isomer (R,CIS) or (R,TRANS) in 2 ml of dichloromethane and added to 1.86 ml 0,2N hydrochloric acid in diethyl ether. After evaporation to dryness of the reaction environment absorb diethyl ether and triturated. The resulting precipitate is centrifuged and washed with diethyl ether. The resulting hydrochloride is dried over P2About5under reduced pressure. Get 0,095 g hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2,dihydro-1 N-tetrazol-5-yl)cyclohexanamine in the form of a pure isomer (R,CIS) or (R,TRANS).

Tplate=S; M+N+=586;

Example 20: HydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyridin-2-repentin-4-amine(compound No. 127)

20.1: 8-pyridine-2-yl-1,4-dioxa-8 azaspiro[4.5]decane.

Place of 1.35 ml of 1,4-dioxa-8 azaspiro[4.5]decane in the presence of 4.54 ml of 2-herperidin in a sealed tube. After carrying out the reaction in a microwave oven at a power of 100 W and a temperature of 150C for 15 minutes, hydrolyzing the product and add dichloromethane. Wednesday then alkalinized 1N aqueous solution of sodium hydroxide. Extracted with dichloromethane until the depletion of the water environment. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic, elwira with a gradient of methanol in dichloromethane, varying from 0% to 2%. Obtain 1.6 g of 8-pyridine-2-yl-1,4-dioxa-8 azaspiro[4.5]decane.

20.2: 1-pyridine-2-reparacin-4-one.

Placed 1.6 g of 8-pyridine-2-yl-1,4-dioxa-8 azaspiro[4.5]decane in 6N aqueous solution of hydrochloric acid. The reaction medium is heated at 60C for 24 hours. After cooling hydrolyzing with sodium carbonate to establish a pH of 8. Extracted with dichloromethane until the depletion of the aqueous phase. After drying over MgSO4and concentration DOS the ha gain of 2.23 g of 1-pyridine-2-reparacin-4-it, used without purification in the subsequent syntheses.

20.3:N{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyridin-2-reparacin-4-amine.

Solubilizing 0.3 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, in 7 ml of dichloromethane in the presence of 0.25 g of 1-pyridine-2-reparacin-4-she received at the stage 20.2. Then add in nitrogen atmosphere 0,22 g triacetoxyborohydride sodium. Stirring is maintained for 18 hours at room temperature. After hydrolysis with a saturated aqueous solution of sodium bicarbonate medium is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/acetone/methanol gradient from 100/0/0 to 90/10/1. Obtain 0.4 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyridin-2-reparacin-4-amine.

20.4: hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyridin-2-repentin-4-amine.

Place of 0.58 gN{(1R)-1-(4-Chlorobenzyl)-2-[4-CEC is hexil-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyridin-2-reparacin-4-amine in 2 ml of dichloromethane and add 3,47 ml 0,2N hydrochloric acid in diethyl ether. After evaporation to dryness of the reaction environment absorb diethyl ether and triturated. The residue is centrifuged and washed with diethyl ether. The resulting hydrochloride is dried over P2About5under reduced pressure. Get 0,37 g hydrochlorideN{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyridin-2-reparacin-4-amine.

Tplate>S; M+N+=593; [α]D20=+14,3(0,938 g/100 ml, DMSO).

Example 21: Hydrochloride 3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-6-fluoro-1,3-benzoxazol-2(3N-she(compound No. 167)

21.1: 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)-5-terfenol.

Placed 2.5 g of 1,4-dioxaspiro[4.5]decane-8-she's in 78 ml of acetic acid. Add 2.0 g of 2-amino-5-terfenol, 10.0 g of triacetoxyborohydride sodium and 11.2 g of sodium sulfate. The reaction medium is stirred for 24 hours at room temperature. After evaporation of the acetic acid residue absorb 1N aqueous solution of sodium hydroxide. Extracted with ethyl acetate to depletion of the aqueous phase. After drying over MgSO4and concentration to dryness, the scientists crude product is crystallized in heptane. The obtained crystals are centrifuged and washed with heptane. Obtain 1.8 g of 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)-5-terfenol.

21.2: 4-[(4-fluoro-2-hydroxyphenyl)amino]cyclohexanone.

Placed 1.8 g of 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)-5-terfenol in 6N aqueous solution of hydrochloric acid. The reaction medium is heated at 60C for 18 hours. After cooling hydrolyzing an aqueous solution of sodium hydroxide to establish a pH of 8. Extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane, varying from 0% to 10%. Receive 1 g of the compound that chromatographic in a mixture of heptane/ethyl acetate gradient from 8/2 to 4/6. Obtain 0.64 g of 4-[(4-fluoro-2-hydroxyphenyl)amino]cyclohexanone.

21.3: 6-fluoro-3-(4-oxocyclohexyl)-1,3-benzoxazol-2(3N)-he.

Solubilizing 0.24 g of 4-[(4-fluoro-2-hydroxyphenyl)amino]cyclohexanone in 11 ml of anhydrous dichloromethane and added 0.27 g of carbonyldiimidazole. The reaction medium is stirred for 18 hours at room temperature. After further adding 0.05 g of carbonyldiimidazole the stirring is continued for 5 hours. After evaporation to dryness extracted with ethyl acetate to IP is osenia the aqueous phase. The organic phase is washed with saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane, varying from 0% to 5%. Obtain 0.3 g of 6-fluoro-3-(4-oxocyclohexyl)-1,3-benzoxazol-2(3Nit.

21.4: 3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-6-fluoro-1,3-benzoxazol-2(3N)-he.

Solubilizing 0.5 g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, in 7 ml of dichloromethane in the presence of 0.29 g of 6-fluoro-3-(4-oxocyclohexyl)-1,3-benzoxazol-2(3Nit obtained at the stage of 21.3. Then added under nitrogen atmosphere and 0.37 g of triacetoxyborohydride sodium. Stirring is maintained for 18 hours at room temperature. After evaporation to dryness and hydrolysis medium is extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/ethyl acetate/methanol gradient from 100/0/0 to 7/2/1. Obtain 0.24 g and 0.2 g of 3-[4-({(1R)-1-(4-chlorbenzyl is)-2-[4-cyclohexyl-4-(1 H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-6-fluoro-1,3-benzoxazol-2(3Nit is in the form of stereoisomers (R,CIS) and (R,TRANS) is not installed configuration.

21.5: hydrochloride 3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-6-fluoro-1,3-benzoxazol-2(3Nit.

Place of 0.15 g of 3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-6-fluoro-1,3-benzoxazol-2(3N)-it is in the form of a pure stereoisomer (R,CIS) or (R,TRANS) in 2 ml of dichloromethane and add 2,23 ml 0,2N hydrochloric acid in diethyl ether. After evaporation to dryness of the reaction environment absorb the ethyl acetate and pound. The residue is centrifuged and washed with ethyl acetate. The resulting hydrochloride is dried over P2About5under reduced pressure. Obtain 0.10 g of the hydrochloride of 3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-6-fluoro-1,3-benzoxazol-2(3N)-it is in the form of a pure stereoisomer (R,CIS) or (R,TRANS).

Tplate=S; M+N+=664.

Example 22: Hydrochloride, 2-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-fluoro-N,Ndime is ilasamaja (compound No. 182)

22.1: methyl-2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)-5-perbenzoate.

Put 4.1 g of 1,4-dioxaspiro[4.5]decane-8-she's in 88 ml of acetic acid. Add 3.0 g of methyl ester of 2-amino-5-fermenting acid, 11.3 g of triacetoxyborohydride sodium and 12.6 g of sodium sulfate. The reaction medium is stirred for 18 hours at room temperature. After the introduction of the additional portion 1,4-dioxaspiro[4.5]decane-8-it is in the amount of 1.5 g and stirring for 24 hours, the acetic acid is evaporated. The residue is treated with 3N aqueous solution of sodium hydroxide. Extracted with ethyl acetate to depletion of the aqueous phase. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira with a gradient of methanol in dichloromethane, varying from 0% to 5%. Get to 0.67 g of methyl 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)-5-perbenzoate.

22.2: 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)-5-Formentera acid.

Put 0.65 g of methyl 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)-5-perbenzoate in 21 ml of methanol and add to 8.3 ml of 1N aqueous sodium hydroxide solution. After adding 5 ml of tetrahydrofuran and heated at 70C for 2 hours 30 minutes, the medium is acidified to pH 2-3 1N aqueous solution of hydrochloric acid. Extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with saturated aqueous what astora sodium chloride, dried over MgSO4and concentrate to dryness. Gain of 0.58 g of 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)-5-fermenting acid, which is used without purification in the subsequent syntheses.

22.3: 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)-5-fluoro-N,N-dimethylbenzamide.

Place of 0.58 g of 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)-5-fermenting acid, obtained in stage 22.2, in 20 ml of dichloromethane in the presence of 0.8 g of dimethylamine hydrochloride, 0.27 g of hydroxybenzotriazole, of 0.38 g of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 2.4 ml of diisopropylethylamine. The mixture is stirred for 48 hours at room temperature. After evaporation to dryness and hydrolysis 1N aqueous solution of sodium hydroxide medium is extracted with dichloromethane until the depletion of the aqueous phase. The organic phase is washed with saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic, elwira with a gradient of methanol in dichloromethane, varying from 0% to 10%. Obtain 0.4 g of 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)-5-fluoro-N,N-dimethylbenzamide.

22.4: 5-fluoro-N,N-dimethyl-2-[(4-oxocyclohexyl)amino]benzamide.

Place of 0.38 g of 2-(1,4-dioxaspiro[4.5]Dec-8-ylamino)-5-fluoro-N,N-dimethylbenzamide 1.7 ml of 2N aqueous hydrochloric acid and stirred at 40C for 2 hours. After concentration to dryness ostate the absorb 1N aqueous solution of sodium hydroxide and then extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic, elwira with a gradient of methanol in dichloromethane, varying from 0% to 10%. Obtain 0.25 g of 5-fluoro-N,N-dimethyl-2-[(4-oxocyclohexyl)amino]benzamide.

22.5: 2-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide.

Solubilizing 0,35g (2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1H1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-1-oxoprop-2-amine, obtained in stage 1.7, in 4 ml of dichloromethane in the presence of 0.25 g of 5-fluoro-N,N-dimethyl-2-[(4-oxocyclohexyl)amino]benzamide are obtained at the stage of 22.4. Then add in nitrogen atmosphere 0,22 g triacetoxyborohydride sodium. Stirring is maintained for 18 hours at room temperature. After concentration to dryness and hydrolysis 1N aqueous solution of sodium hydroxide medium is extracted with ethyl acetate to depletion of the aqueous phase. The organic phase is washed with water, then saturated aqueous sodium chloride. After drying over MgSO4and concentration to dryness, the resulting crude product chromatographic on silica gel, elwira a mixture of dichloromethane/ethyl acetate/methanol gradient from 100/0 to 7/2,5/0,5. Get 0,22 g and 0.1 g of 2-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide in the form of stereoisomers (R,CIS) and (R,TRANS) is not installed configuration.

22.6: hydrochloride, 2-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide.

Put 0,22 g 2-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide in the form of a pure stereoisomer (R,CIS) or (R,TRANS) in 2 ml of dichloromethane and add 3,15 ml 0,2N hydrochloric acid in diethyl ether. After concentration to dryness of the reaction environment absorb the ethyl acetate and pound. The residue is centrifuged and washed with ethyl acetate. The resulting hydrochloride is dried over P2About5under reduced pressure. Get to 0.19 g of the hydrochloride of 2-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide in the form of a pure stereoisomer (R,CIS) or (R,TRANS).

Tplate=S; M+N+=692

The table below illustrates the chemical structure and the physical is their properties of some compounds according to the invention, in particular, compounds of formula (I bis), corresponding to compounds of formula (I)in which R1means tsiklogeksilnogo group, R2refers to a group of 1,2,4-triazolyl, and Ra=Ra'=R5=H, n=1 and R3denotes a chlorine atom, located in the para-position on the phenyl cycle to which it is attached.

In the table below:

the carbon atom carrying the group of 4-Cl-benzyl, has the configuration (R),

- in the column "salt" the sign "-" denotes a compound in the form of free base, whereas "HCl" represents a compound in hydrochloride, and "CF3COOH - connection triptoreline,

- "TPL" refers to melting point connections

- Me, Et, tBu and Bn denote, respectively, the groups methyl, ethyl, tert-butyl and benzyl.

Table

* isomer (CIS or TRANS)
** the configuration is CIS or TRANS is not installed, the arbitrary image

The table below illustrates the chemical structure and physical properties of some compounds according to the invention, in particular compounds of formula (I ter), corresponding to compounds of formula (I)in which R1means tsiklogeksilnogo group, R2refers to a group of 1,2,4-triazolyl, and Ra=Ra'=R5=H, n=1, and R3denotes a chlorine atom, located in the para-position on the phenyl cycle to which it is attached.

In the table below:

the carbon atom carrying the group of 4-Cl-benzyl, has the configuration (S),

- in the column "salt" sign "HCl" represents a compound in hydrochloride,

- "TPL" refers to the melting point of the connection.

Compounds according to the invention were farmacologicas research to study the agonistic action on receptors melanocortins, in particular, agonistic action at the receptor MS and/or MS.

Determination of the affinity of the compounds of formula (I) according to the invention with receptors MS and MS.

This test on the affinity was carried out by measuring the binding of the ligand [125I]-[Nle4, D-Phe7]-α-MSH with cellular membranes: the displacement of the radioactive ligand used for the identification of inhibitors of specific binding to recombinant melanocortin receptors.

In this experiment, the used membranes obtained from cells Cho-K1 expressing the receptor for human MS high density (Euroscreen) or acquired membrane (Perkin Elmer Life Sciences, Receptor Biology) cells HEK-293 expressing receptors hMC3. Cells Cho-K1, transfetsirovannyh using receptor gene hMC4 (Euroscreen), was planted in culture medium DMEM/Nutrient Mix F12 containing 10% bovine serum (Biowhittaker), 1% sodium pyruvate, 1% L-glutamine, 1% non-volatile amino acids, 0.4 mg/ml geneticin (G418) and 0.5% PenStrep, these products were obtained from Gibco/BRI, except bovine serum. The cells were scraped off at 80%confluently, and cell sediments were frozen at-80C.

Tubes with cells (about 70×106cells) were thawed on ice and re-suspended in 10 ml of binding buffer [25 mm HEPES, pH 7.0, 1 mm MgCl2, 1.5 mm CaCl2, 100 mm NaCl, 1 mm 1,10-phenanthroline and 1 tablet CompleteTR(protease inhibitor Roche) in 50 ml buffer] using device Polytron within 20 seconds. The suspension was centrifuged for 20 minutes at speed 19500 rpm at 4C. The supernatant was discarded and the precipitate again suspended in 5 ml of binding buffer. Using the the Bradford protein content was determined, available in the sample, and drove concentration of 3 µg/25 µl dilution in binding buffer.

Ligand [125I]-[Nle4, D-Phe7]-α-MSH was diluted in binding buffer+0.2% BSA. The SPA beads (agglutinin wheat polyvinyltoluene, Amersham Pharmacia Biotech)was hydrational in binding buffer+0.2% BSA and then mixed with the homogenate of cells with 3 μg of cellular protein and 250 μg of beads in 50 ál. Investigational products (dissolved in 10%DMSO) in an amount of 10 μl at a concentration of 10 times the final concentration, were placed in a white 96-well plate with clear bottom (CORNING 3604 Polystyrene Non-Binding Syrface). Nonspecific binding was determined using NDP-αMSH at a concentration of 10-7Meters of Total binding was measured by the number of pulses per minute in the presence only of the radioactive ligand. The distribution of a suspension of membranes with beads (50 µl/well) was monitored on the distribution of the solution of [125I]-[Nle4, D-Phe7]-α-MSH 40 µl/well (100 PM final concentration) in final volume of 100 µl/well. After 6-hour incubation at room temperature was carried out by counting on scillations counter Microbeta TriLux. The value of the IC50compounds represents the concentration that reduces by 50% the specific binding with the displacement of the radioactive ligand.

Thus, it was determined that compounds the ia according to the invention have an affinity with receptors MS and/or MS. The values of the IC50these compounds against the receptors MS and MS were below 10 μm, most compounds of this value was in the range of 1 nm-1 μm. For example, compounds No. 1, 2 and 12 of the table had values IC50accordingly equal to 0.25 μm, of 0.57 μm and 0.20 μm on onoshenie receptor MS.

The definition of agonistic activity of the compounds of formula (I) according to the invention in relation to the receptors MS and MS.

This functional test is used to distinguish agonistic activity and antagonistic activity. This was determined by the formation of cyclic adenosine monophosphate (camp)produced during activation of the receptor MS or receptor MS.

Cells Cho-K1 expressing the receptor for human MS average density (Euroscreen), was planted in culture medium DMEM/Nutrient Mix F12 (Gibco/BRI)containing 10% bovine serum, 0.5% sodium pyruvate, 1% L-glutamine, 1% non-volatile amino acids, 200 mg/l of hygromycin In 0.5% PenStrep, these products were obtained from Gibco/BRI, except bovine serum (Biowhittaker) and hygromycin (Sigma).

Cells CHO (dhfr-), espressione receptor human MS, was planted in the culture medium MEM Eagle (Sigma)containing 10% cialisbuynow bovine serum, 1% L-glutamine, 1% sodium pyruvate, 20 mg/500 ml L-Proline, 0.3 mg/ml geneticin and 0.5% PenStrep, these products were obtained from Gibco/BRI, except on ilizovano bovine serum (Cambrex) and L-Proline (Sigma).

The compounds (diluted in 10%DMSO) in an amount of 10 μl at a concentration exceeding 10 times the final concentration, was placed on the cell plates (final volume=100 ál/well). After incubation for 1 hour (C, 5% CO2) analyzed the content of camp using kits TROPIX (Appelera) in accordance with the supplier's instructions. The inherent connections activity was estimated by comparing the stimulation of the production of camp produced by the studied compounds, stimulation induced nm NDP-αMSH (100% maximum). Is EU50compounds represents the concentration at which celebrated 50% of the maximal stimulation achieved by this connection.

Thus, it was found that the compounds according to the invention are agonists receptarea MS and/or MS. They have values EU50in relation to the receptors MS and MS below 10 μm, most compounds of this value is from 1 nm to 1 μm. For example, compounds No. 1 and 2 in the table have values EU50,respectively equal to 590 nm and 370 nm against the receptor MS and 80 nm and 30 nm with respect to the receptor MS.

Compounds according to the invention have an agonistic activity against receptor melanocortin, and therefore they can be used to obtain Lekarstvo what x means. Thus, according to one aspect, the invention relates to pharmaceuticals which contain a compound of the formula (I) or additive salt of this compound with a pharmaceutically acceptable acid, or a hydrate or MES the compounds of formula (I).

These medicines can find use in the treatment of pathologies involving receptors melanocortins, in particular, receptors MS and/or MS: it is, in particular, on the treatment and prevention of obesity, diabetes and sexual disorders that can affect both sexes, such as erectile dysfunction, cardiovascular diseases such as myocardial infarction or hypertension, and also be used with anti-inflammatory treatment or in the treatment of alcohol dependence.

According to another aspect of the present invention relates to pharmaceutical compositions containing as active principle a compound according to the invention. These pharmaceutical compositions contain an effective dose of at least one compound according to the invention or a pharmaceutical salt or hydrate or MES specified connection, and at least one pharmaceutically acceptable excipient. These excipients selected depending on the pharmaceutical form and the desired method of administration, and choose from among the ordinary is x excipients, well-known specialist.

In the pharmaceutical compositions according to the present invention, intended for pearling, sublingual, transcutaneous, intramuscular, intravenous, topical or local application for admission through the trachea or through the nose, transdermal or rectal administration, the active principle of formula (I)described above, or its salt, MES or perhaps hydrate can be entered in a single form in a mixture with classical pharmaceutical excipients animal or person for the purpose of prevention or treatment of disorders or diseases mentioned above.

Suitable single form, provided for the introduction, include forms for oral administration such as tablets, hard or soft gelatin capsules, powders, granules and solutions or suspensions for oral administration, forms for admission under the tongue or sucking the cheek, for insertion through the trachea through the nose or eye, forms for inhalation, forms for topical application, for trandermal, subcutaneous, intramuscular or intravenous administration, the forms for rectal administration as well as grafts. For topical application it is possible to use the compounds according to the invention in the form of creams, gels, ointments or lotions.

The preferred form of this introduction is oral path.

For example, one form of the introduction of the compounds according to the invention in the form of tablets may contain the following components:

The connection according to the invention 50 mg

Beckons 223,75 mg

Croscarmellose sodium 6.0 mg

Corn starch 15,0 mg

The hypromellose of 2.25 mg

Magnesium stearate 3.0 mg

Can occur in special situations, when the dose should be increased or reduced; these doses are also included in the scope of the invention. According to common practice necessary for each patient, the dose is determined by the physician depending on the method of administration, the body weight of the patient and their personal reactions.

According to another aspect of the invention relates also to a method of treating the pathologies indicated above which comprises the administration to the patient an effective amount of the compounds according to the invention or its pharmaceutically acceptable salt or hydrate or solvate.

1. The compound corresponding to the formula (I):

in which n is 1,
Ra, Ra', Rb, Rb', be otherness or different, denote a hydrogen atom or an alkyl or cycloalkyl group, and Rband Rb'may form together with the carbon atoms of the cycle to which they are attached, carbon bridge, containing 4 link,
R1means tsiklogeksilnogo group,
R2putting the AET 1,2,4-triazolyl group,
R3denotes 1-3 groups selected from halogen atoms, in any position of the cycle to which they are attached,
R5denotes a hydrogen atom,
R4choose from the groups of formulae (a), (b) and (c)below, a mono - or polyamidine aryl group:

in which p=0, 1, 2 or 3, m=0, 1, or 2, and either
a) X represents the group-N(R10)-where
R10choose from:
group-CO-NR8R9, -COOR8, -(CH2)x-OR8, -(CH2)x-COOR8, -(CH2)x-COR8in which x=1, 2, 3,or 4
geteroseksualnoe group condensed with an aryl group, cycloalkyl, aryl, heteroaryl, alcylaryl, -CO-alkyl, -CO-cycloalkyl-WITH-geteroseksualnoe, -CO-aryl, CO-heteroaryl, -CO-alcylaryl, -SO2-alkyl, -SO2-cycloalkyl, -SO2-aryl,
moreover alkyl, cycloalkyl, heterocytolysine, aryl or heteroaryl group optionally substituted by one or more groups selected from halogen atoms and the groups R, R', OR, NRR', -CN, -COOR, COR;
or R10together with the nitrogen atom to which it is attached and with the carbon atom located in any position of the cyclic structure of the formula (a), but not in the neighboring position to the criminal code is related to the nitrogen atom, forms a bridge containing 3-5 units, R8and R9choose, independently from each other, from a hydrogen atom and alkyl or cycloalkyl groups;
R and R' denote, independently of one another, a hydrogen atom or alkyl, cycloalkyl, aryl group;
or
b) X denotes the group-C(R6)(R7)-where
R6choose from:
hydrogen atom, halogen atom,
group -(CH2)x-OR8, -(CH2)x-COOR8, -(CH2)x-NR8R9-(CH2)x-CO-NR8R9or
-(CH2)x-NR8-COR9in which x=0, 1, 2, 3,or 4
alkyl, cycloalkyl, geteroseksualnoe, aryl, heteroaryl, alcylaryl, alkylchlorosilanes group,
geteroseksualnoe group, condensed or neskondensirovannyh located in Spiro-position to the cycle of the formula (a), to which it is attached,
geteroseksualnoe group condensed with an aryl group, and alkyl, cycloalkyl, heterocytolysine, aryl or heteroaryl group optionally substituted by one or more groups selected from halogen atoms and the groups R, R', OR, NRR', -CO - NRR', -CN, -COOR, OCOR, COR, NRCOOR'; and
heterocytolysine group optionally condensed with an aryl group;
R7chosen from hydrogen atoms and halogen and alkyl, cyclo is skilnik, aryl, heteroaryl, alcylaryl, alkylglycerols groups, -OR, -O-aryl, -O-alcylaryl, -O-alkylglycerols, group-NRR', -CO-NRR', -NR-CO-R', -NR-CO-NRR', -NR-COOR', -NO2, -CN, and-COOR,
R8and R9choose, independently from each other, from a hydrogen atom and alkyl, cycloalkyl, geterotsiklicheskikh, aryl, heteroaryl, alcylaryl, alkylglycerols groups, -CO-alkyl, -CO-cycloalkyl, -CO-aryl, -(CH2)x-OR, where x=0, 1, 2, 3 or 4, and alkyl, cycloalkyl, heterocytolysine, aryl and heteroaryl groups are optionally substituted by one or more groups selected from halogen atoms and the groups R, R', OR, NRR', -CO-NRR', -CN, -COOR, OCOR, COR, NRCOOR';
or R8and R9form together cycloalkyl or heteroseksualci;
R and R' denote, independently of one another, a hydrogen atom or alkyl, cycloalkyl, geterotsyklicescoe, aryl, or together can form cycloalkyl or heteroseksualci;
when the heteroaryl group is an aromatic group containing from 5 to 10 atoms and containing from 1 to 4 heteroatoms selected from nitrogen, oxygen, or sulfur;
heterocytolysine group is cycloalkyl group containing from 5 to 10 atoms and containing from 1 to 4 heteroatoms selected from nitrogen, oxygen, or sulfur;
as based what I or an acid additive salt, and also in the form of a hydrate or of MES.

2. The compound of formula (I) according to claim 1, wherein R4choose from the groups of formulae (a), (b) and (C), possibly mono - or polyamidine aryl group, in which X denotes the group-C(R6)(R7)-in which
R6choose from:
hydrogen atom,
group -(CH2)x-OR8, -(CH2)x-COOR8, -(CH2)x-NR8R9-(CH2)x-CO-NR8R9or
-(CH2)x-NR8-COR9in which x=0, 1, 2, 3,or 4
alkyl, cycloalkyl, geteroseksualnoe, aryl, heteroaryl, alcylaryl, alkylchlorosilanes group, geteroseksualnoe group in Spiro to a cycle of formula (a), to which it is attached,
geteroseksualnoe group condensed with an aryl group,
R7chosen from hydrogen atoms and halogen and alkyl, cycloalkyl, aryl, heteroaryl, alcylaryl, alkylchlorosilanes group, -OR, -O-aryl, -O-heteroaryl, -O-alcylaryl, group-NRR', -CO-NRR', -NR-CO-R', -NR-CO-NRR', -NR-COOR', -NO2, -CN, and-COOR, R8and R9choose, independently from each other, from a hydrogen atom and alkyl, cycloalkyl, geterotsiklicheskikh, aryl, heteroaryl, alcylaryl, alkylglycerols groups, -CO-alkyl, -CO-cycloalkyl, -CO-aryl, and -(CH2)x -OR, where x=0, 1, 2, 3,or 4
R and R' denote, independently of one another, a hydrogen atom or alkyl, cycloalkyl, geterotsyklicescoe, aryl group.

3. The compound of formula (I) according to claim 1, wherein R4choose from the groups of formulae (a), (b) and (c), in which X denotes the group-C(R6)(R7)-, in which R6is selected from a halogen atom or cycloalkyl or geteroseksualnoe group Spiro-position to the cycle of the formula (a), to which it is attached.

4. The compound of formula (I) according to claim 1, wherein R4choose from the groups of formulae (a), (b) and (c), in which X denotes the group-C(R6)(R7)-, in which alkyl, cycloalkyl, heterocytolysine, aryl or heteroaryl group optionally substituted by 1 or more groups selected from R or R', OCOR, COR, OCONRR', NRCOOR'.

5. The compound of formula (I) according to claim 1, wherein R4choose from the groups of formulae (a), (b) and (C), in which X denotes the group-C(R6)(R7)-in which heterocytolysine group optionally condensed with an aryl group.

6. The compound of formula (I) according to claim 1, wherein R4selected from groups of the formulas (a), (b) and (c), where X denotes the element of C(R6)(R7)-, in which R8and R9selected, independently of one another, from alkyl, cycloalkyl, heterocycle skilnik, aryl and heteroaryl groups optionally substituted by one or more groups selected from R, R', OCOR, COR, OCONRR', NRCOOR',
or R8and R9form together cycloalkyl or heteroseksualci.

7. The compound of formula (I) according to claim 1, wherein R4selected from groups of the formulas (a), (b) and (C), in which X denotes the group-C(R6)(R7)-, in which R and R' may form together cycloalkyl or heteroseksualci.

8. The compound of formula (I) according to claim 1, wherein R7is hydrogen.

9. The compound of formula (I) according to claim 1, wherein R4denotes a group of formula (a), in which p=2, is described below:

10. The compound of formula (I) according to claim 1, wherein R4selected from groups of the formulas (a), (b) and (C), optionally mono - or polyamidine aryl or heteroaryl group, in which X represents the group-N(R10)-, in which:
R10chosen from:
group-CO-NR8R9, -COOR8,
group -(CH2)x-OR8, -(CH2)x-COOR8, -(CH2)x-NR8-COR9in which x=1, 2, 3,or 4
geteroseksualnoe group condensed with an aryl group, group cycloalkyl, aryl, heteroaryl, alcylaryl, -CO-cycloalkyl, -CO-geteroseksualnoe, -CO-heteroaryl, -CO-alcylaryl, -SO2-alkyl is Noah, -SO2-cycloalkyl, -SO2-aryl;
or R10forms together with the nitrogen atom to which it is attached and with the carbon atom located in any position of the cyclic structure of the formula (a), but not in the neighboring position to the specified nitrogen, the bridge containing 3-5 links;
R8and R9selected, independently from each other, from a hydrogen atom and alkyl groups, cycloalkyl,
R and R' denote, independently of one another, a hydrogen atom or alkyl, cycloalkyl, aryl group.

11. The compound of formula (I) according to claim 1, wherein R4selected from groups of the formulas (a), (b) and (C)optionally substituted by exography, in which X represents the group-N(R10).

12. The compound of formula (I) according to claim 1, wherein R4selected from groups of the formulas (a), (b) and (C), in which X represents the group-N(R10), in which R8and R9selected independently of one another, denote alkyl or cycloalkyl group.

13. The compound of formula (I) according to claim 1, wherein R4selected from groups of the formulas (a), (b) and (C), in which X represents the group-N(R10), in which R10represents -(CH2)x-COR8in which x=1, 2, 3, or 4.

14. The compound of formula (I) according to claim 1, wherein R4selected from groups of the formulas (a), (b) and (C), in which X represents the group-N(R10), in which Alkalyn is e, cycloalkyl, heterocytolysine, aryl or heteroaryl group optionally substituted by 1 or more groups selected from R or R', COOR, COR.

15. The compound of formula (I) according to claim 1, wherein R4selected from groups of the formulas (a), (b) and (C), in which X represents the group-N(R10), in which heterocytolysine group optionally condensed with an aryl group.

16. The compound of formula (I) according to claims 1, 10, or 15, characterized in that R4denotes a group of formula (a), in which p=2, is described below:

17. The compound of formula (I) according to claim 1, wherein R2means cycloalkyl group in the form of a base or an acid additive salt, and also in the form of a hydrate or of MES.

18. The compound of formula (I) according to claim 1, wherein R2means triazolyl group in the form of a base or an acid additive salt, and also in the form of a hydrate or of MES.

19. The compound of formula (I) according to claim 1, wherein R3denotes 1 to 3 groups, identical or different, chosen from halogen atoms, in the form of a base or an acid additive salt, and also in the form of a hydrate or of MES.

20. The compound of formula (I) according to claim 1, wherein R5denotes a hydrogen atom in the form of a base or an acid additive salt, and also in the form of a hydrate or MES is.

21. The compound of formula (I) according to claim 1, characterized in that:
n=1 and Ra=Ra'=Rb=Rb'=H or
n=1 and Ra=Ra'=H and Rband Rb'together with the carbon atoms of the cycle to which they are attached, form a carbon bridge, containing 4 link, in the form of a base or an acid additive salt, and also in the form of a hydrate or of MES.

22. Compounds with the following names:
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2-phenylethyl)piperidine-4-amine,
4-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]phenol,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-8-methyl-8-azabicyclo[3.2.1]Octan-3-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-phenylpiperidine-4-amine,
1-benzoyl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl }PIP is ridin-4-amine,
1-acetyl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1,4-dioxaspiro[4.5]Decan-8-amine,
N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N,N-dimethylcyclohexane-1,4-diamine,
4-(aminomethyl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,
3-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-8-methyl-8-azabicyclo[3.2.1]Octan-6-ol,
CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanol,
TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanol,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(TRIFLUOROACETYL)piperidine-4-amine,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-piperidine-1-carboxamide,
CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-phenylcyclohexanol,
TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-phenylcyclohexanol,
CIS-N-{(1R)--(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-forfinal)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-forfinal)cyclohexane-1,4-diamine,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2,2,2-triptorelin,
N-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2,2,2-triptorelin,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]acetamide", she
N-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)cyclohexyl]acetamide", she
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(4-perbenzoic)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(cyclopentanecarbonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(cyclobutanecarbonyl)piperidine-4-amine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-methylcyclohexane-1,4-diamine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(pyridine-2-ylcarbonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triaz the l-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(phenylacetyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(methylsulphonyl)piperidine-4-amine,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-N-methylacetamide,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(1,3-dihydro-2H-isoindole-2-yl)cyclohexanamine,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-cyclohexyl]-N-methylbenzamide,
ethyl-CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylate,
ethyl TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylate,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-phenylcyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-phenylcyclohexane-1,4-diamine, N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N-methyl-N-phenylcyclohexane-1,4-diamine,
N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N-(4-forfinal)-N-methylcyclohexane-1,4-diamine,
CIS - or TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohex the l-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-diethylcarbamyl,
CIS - or TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-diethylcarbamyl,
CIS - or TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-dimethylcyclohexylamine,
CIS - or TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-dimethylcyclohexylamine,
CIS-N-benzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-methylcyclohexanecarboxylic,
TRANS-N-benzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-methylcyclohexanecarboxylic,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine,
CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylic,
TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylic,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}--isonicotinohydrazide-4-amine,
CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)cyclohexanol,
TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)cyclohexanol,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(1-methyl-1H-imidazol-2-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(5-methylisoxazol-3-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(3,4-differentail]piperidine-4-amine,
1-[(1-tert-butyl-5-methyl-1H-pyrazole-3-yl)carbonyl]-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(3,5-dimethylisoxazol-4-yl)carbonyl] piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(3-thienylboronic]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(pyrrolidin-1-ylcarbonyl)piperidine-4-amine,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)-N-phenylpiperidine-1-Carbo who said,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)-N,N-dimethylpiperidin-1-carboxamid,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-amino)-N,N-diethylpiperazine-1-carboxamid,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(piperidine-1-ylcarbonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(morpholine-4-ylcarbonyl)piperidine-4-amine,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-methyl-N-phenylpiperidine-1-carboxamide,
N-benzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-methylpiperidin-1-carboxamid,
N-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-methoxycyclohexanone,
4-[4-(benzyloxy)phenyl]-N-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-cyclohexanamine,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2-methoxyacetate,
2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-2-oxoacetate,
2-(benzyloxy)-N-[CIS-4-({(1R)--(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]acetamide", she
3-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it,
3-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(2-methoxyethyl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}N'-(2-methoxyethyl)cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-morpholine-4-illlogical,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-morpholine-4-illlogical,
1-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]pyrrolidin-2-it,
1-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]pyrrolidin-2-it,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2-methoxyethoxy)cyclohexanamine,
ethyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxylate,
methyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohe the power-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxylate,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2S)-piperidine-2-ylcarbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2R)-piperidine-2-ylcarbonyl]piperidine-4-amine,
CIS-4-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile,
TRANS-4-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile,
1-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperidine-2-it,
1-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperidine-2-it,
N-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]propanamide,
tert-butyl-(2{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-2-oxoethyl)carbamate,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl} amino)cyclohexyl]glycinamide,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2-hydroxyacetamido,
N-[CIS-4-({(1R)-1-(4-chlorobenz the l)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2,2-dimethylpropanamide,
N-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2,2-dimethylpropanamide,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-methoxyphenyl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-methoxyphenyl)cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2H-tetrazol-5-yl)cyclohexanamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2H-tetrazol-5-yl)cyclohexanamine,
2-{[CIS-4-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino} phenol,
2-{[TRANS-4-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}phenol,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexylacetate,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-N,N-dimethylglycinamide,
N2-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl} amino)cyclohexyl]-N,N-dimethylglycinamide,
N2-[CIS-4-({(R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide,
N2-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide,
4-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperazine-2-it,
4-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperazine-2-it,
CIS-4-(4-acetylpiperidine-1-yl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl cyclohexanamine,
TRANS-4-(4-acetylpiperidine-1-yl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyridin-2-reparacin-4-amine,
methyl-N-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinate,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2,2-dottorati)piperidine-4-amine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-chlorophenyl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-chlorophenyl)cyclohexane-1,4-diamine,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-12,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexylphenols,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-2-were)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-2-were)cyclohexane-1,4-diamine,
4-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}benzonitrile,
N-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]cyclopropanecarboxamide,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(6-methylpyridazin-3-yl)piperidine-4-amine,
methyl-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]acetate,
CIS - or TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-(morpholine-4-ylphenyl)cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(2,4-differenl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(2,4-differenl)cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(5-herperidin-2-yl)cyclohexane-1,-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(5-herperidin-2-yl)cyclohexane-1,4-diamine,
N-1H-1,2,3-benzotriazol-5-yl-N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-cyclohexane-1,4-diamine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyrimidine-2-reparacin-4-amine,
1-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]imidazolidin-2-it,
1-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]imidazolidin-2-it,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-cyclopropylidene-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-{[(2S)-4,4-deformability-2-yl]carbonyl}piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4,4-diverticulectomy,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(3,4-differenl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(3,4-differenl)cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,
CIS-N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N-ethyl-N-(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N-ethyl-N-(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-[4-(trifluoromethyl)phenyl]cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-[4-(trifluoromethyl)phenyl]cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-3-were)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-3-were)cyclohexane-1,4-diamine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(4,4-debtor-N-shed)piperidine-4-amine,
1-(1H-benzimidazole-2-yl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl }piperidine-4-amine,
1-(2,1-benzisoxazol-3-ylcarbonyl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ilma who yl)piperidine-1-yl]-2-oxoethyl} piperidine-4-amine,
1-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]butane-2-it,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2,2,2-triptorelin)piperidine-4-amine,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(4-methoxyphenyl)piperidine-1-carboxamide,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(4-forfinal)piperidine-1-carboxamide,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(2,4-differenl)piperidine-1-carboxamide,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(3,4-differenl)piperidine-1-carboxamide,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl)amino)-N-(2-forfinal)piperidine-1-carboxamide,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(2-methoxyphenyl)piperidine-1-carboxamide,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-[4-
(dimethylamino)phenyl]piperidine-1-carboxamide,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(5-fluoro-1H-indol-2-yl)carbonyl]Piperi the Jn-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(pyrazin-2-ylcarbonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(5-phenyl-1,3-oxazol-4-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(isoxazol-5-ylcarbonyl)piperidine-4-amine,
3-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl} amino)cyclohexyl]-6-fluoro-1,3-benzoxazol-2(3H)-he,
3-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-6-fluoro-1,3-benzoxazol-2(3H)-he,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]pyridin-2-carboxamid,
2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-terfenol or
2-{[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-terfenol,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(quinoline-2-ylcarbonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(3-methylpyridin-2-yl)CT is of IMT]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(1H-1,2,4-triazole-3-ylcarbonyl)piperidine-4-amine,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]of-2.1-benzisoxazol-3-carboxamide,
1-(1,3-benzothiazol-2-ylcarbonyl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(6-methylpyridin-2-yl)carbonyl]piperidine-4-amine,
1-(1-benzofuran-2-ylcarbonyl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(6-herperidin-2-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(1-phenyl-1H-pyrazole-5-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2,4-differentail)piperidine-4-amine,
CIS-N-(1,3-benzothiazol-2-ylmethyl)-N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(1,3-thiazol-2-yl is ethyl)cyclohexane-1,4-diamine,
2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide,
2-{[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(6-vinylpyridin-2-yl)carbonyl]piperidine-4-amine,
TRANS-N-(tert-butyl)-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylic,
CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(3,4-differenl)cyclohexanecarboxylic,
CIS-N-{(1S)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,
TRANS-N-{(1S)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine.

23. Compounds with the following names:
4-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]phenol,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexa the -1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}cyclohexane-1,4-diamine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1,4-dioxaspiro[4.5]Decan-8-amine,
N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N,N-dimethylcyclohexane-1,4-diamine,
4-(aminomethyl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,
CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanol,
TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanol,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-phenylcyclohexanone,
CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-phenylcyclohexanol,
TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-phenylcyclohexanol,
CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-phenylcyclohexanecarboxylic, TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-phenylcyclohexanecarboxylic,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-forfinal)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-forfinal)cyclohexane-1,4-diamine,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl)amino)cyclohexyl]-2,2,2-triptorelin,
N-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl] -2,2,2-triptorelin,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]acetamide", she
N-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]acetamide", she
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-methylcyclohexane-1,4-diamine,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-N-methylacetamide,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(1,3-dihydro-2H-isoindole-2-yl)cyclohexanamine,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-illogical-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-N-methylbenzamide,
ethyl-CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylate,
ethyl TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylate,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(trifluoromethyl)cyclohexanamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(trifluoromethyl)cyclohexanamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-phenylcyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-phenylcyclohexane-1,4-diamine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2,5-dimethyl-2,5-dihydro-1H-pyrrol-1-yl)cyclohexanamine,
N-benzyl-N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N-methylcyclohexane-1,4-diamine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-pyrrolidin-1-illlogical,
2-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}ethanol,
2-{benzyl[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-t is eazol-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}ethanol,
N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N-methyl-N-phenylcyclohexane-1,4-diamine,
N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N-(4-forfinal)-N-methylcyclohexane-1,4-diamine,
CIS - or TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexylcarbonyl acid,
CIS - or TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexylcarbonyl acid,
CIS - or TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-diethylcarbamyl,
CIS - or TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-diethylcarbamyl,
CIS - or TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-dimethylcyclohexylamine,
CIS - or TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-dimethylcyclohexylamine.

24. Compounds with the following names:
CIS-N-benzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-methylcyclohexanecarboxylic,
TRANS-N-benzyl-4-({(R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-methylcyclohexanecarboxylic,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(3-methyl-1,2,4-oxadiazol-5-yl)cyclohexanamine,
CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylic,
TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarboxylic,
CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)cyclohexanol,
TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-1-(4-forfinal)cyclohexanol,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-methoxycyclohexanone,
4-[4-(benzyloxy)phenyl]-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,
4-(benzyloxy)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2-methoxyacetate,
2-(benzyloxy)-N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclo is exil-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]acetamide", she
3-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it,
3-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-1,3-oxazolidin-2-it,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(2-methoxyethyl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(2-methoxyethyl)cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-morpholine-4-illlogical,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-morpholine-4-illlogical,
1-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]pyrrolidin-2-it,
1-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)yclohexanol] pyrrolidin-2-it,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2-methoxyethoxy)cyclohexanamine,
CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile,
TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohe the power-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexanecarbonitrile,
1-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperidine-2-it,
1-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperidine-2-it,
N-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]propanamide,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2-hydroxyacetamido,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2,2-dimethylpropanamide,
N-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-2,2-dimethylpropanamide,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-methoxyphenyl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-methoxyphenyl)cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2H-tetrazol-5-yl)cyclohexanamine,
TRANS-N-{(1R)-1-(4-chlorobenz the l)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4-(2H-tetrazol-5-yl)cyclohexanamine,
2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino} phenol,
2-{[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl] amino}phenol,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]acetate,
N2-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-N,N-dimethylglycinamide,
N2-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]-N,N-dimethylglycinamide,
N2-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide,
N2-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinamide,
4-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperazine-2-it,
4-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]piperazine-2-it,
CIS-4-(4-acetylpiperidine-1-yl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexanamine,
TRANS-4-(acetylpiperidine-1-yl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl} cyclohexanamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-chlorophenyl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-chlorophenyl)cyclohexane-1,4-diamine,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl} amino)cyclohexylphenols,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-2-were)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-2-were)cyclohexane-1,4-diamine,
4-{[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}benzonitrile,
N-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]cyclopropanecarboxamide,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(2,4-differenl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(2,4-differenl)cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(5-herperidin-2-yl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(5-herperidin-2-yl)cyclohexane-1,4-diamine,
N-1H-1,2,3-benzotriazol-5-yl-N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,
1-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]imidazolidin-2-it,
1-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl] imidazolidin-2-it,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(3,4-differenl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(3,4-differenl)cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1N-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,
CIS-N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N-ethyl-N-(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N-ethyl-N-(4-fluoro-3-methoxyphenyl)cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'[4-(trifluoromethyl)phenyl]cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-[4-(trifluoromethyl)phenyl]cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-3-were)cyclohexane-1,4-diamine,
TRANS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-fluoro-3-were)cyclohexane-1,4-diamine,
3-[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl)amino)cyclohexyl]-b-fluoro-1,3-benzoxazol-2(3H)-he,
3-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl)amino)cyclohexyl]-6-fluoro-1,3-benzoxazol-2(3H)-he,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]pyridin-2-carboxamid,
2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-terfenol, or
2-{[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-terfenol,
N-[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]of-2.1-benzisoxazol-3-carboxamide,
CIS-N-(1,3-benzothiazol-2-ylmethyl)-N'-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-Tr the azole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl} cyclohexane-1,4-diamine,
CIS-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(1,3-thiazol-2-ylmethyl)cyclohexane-1,4-diamine,
2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide,
2-{[TRANS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-5-fluoro-N,N-dimethylbenzamide,
TRANS-N-(tert-butyl)-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]cyclohexanecarboxylic,
CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(3,4-differenl)cyclohexanecarboxylic,
CIS-N-{(1S)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine,
TRANS-N-{(1S)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}cyclohexane-1,4-diamine.

25. Compounds with the following names:
2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-2-oxoacetate,
tert-butyl(2-{[CIS-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]amino}-2-oxoethyl)carbamate,
CIS-or TRANS-N-{(1R)-1-(4-chlorobenz the l)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-N'-(4-(morpholine-4-ylphenyl)cyclohexane-1,4-diamine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-4,4-diverticulectomy.

26. Compounds with the following names:
1-benzyl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2-phenylethyl)piperidine-4-amine,
2-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]ethanol,
3-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]propan-1-ol,
4-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]butane-1-ol,
tert-butyl 4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxylate,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-8-azabicyclo[3.2.1]Octan-3-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-8-methyl-8-azabicyclo[3.2.1]Octan-3-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-9-methyl-9-azabicyclo[3.2.1]nonan-3-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidin the-1-yl]-2-oxoethyl}Hinkley-3-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}azepin-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-3-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-phenylpiperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[3-cyclohexyl-3-(1H-1,2,4-triazole-1-ylmethyl)-8-azabicyclo[3.2.1]Oct-8-yl]-2-oxoethyl}piperidine-4-amine,
1-benzyl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}pyrrolidin-3-amine,
1-benzoyl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,
1-acetyl-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl] -2-oxoethyl} piperidine-4-amine,
3-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-8-methyl-8-azabicyclo[3.2.1]Octan-6-ol,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(TRIFLUOROACETYL)piperidine-4-amine,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxamide,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(4-perbenzoic)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-elmet the l)piperidine-1-yl]-2-oxoethyl}-1-(cyclopentanecarbonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(cyclobutanecarbonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(4-were)sulfonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(pyridine-2-ylcarbonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(phenylacetyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(methylsulphonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-2-phenylpiperidine-4-amine,
(1S,3R,5S,7S)-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)adamantane-1-ol.

27. Compounds with the following names:
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-isonicotinohydrazide-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(1-methyl-1H-imidazol-2-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(5-methyl-isoxazol-3-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Harbin who yl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(3,4-differentail)piperidine-4-amine,
1-[(1-tert-butyl-5-methyl-1H-pyrazole-3-yl)carbonyl]-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl} piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(3,5-dimethylisoxazol-4-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(3-thienylboronic)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(pyrrolidin-1-ylcarbonyl] piperidine-4-amine,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-phenylpiperidine-1-carboxamide,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-dimethylpiperidin-1-carboxamid,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N,N-diethylpiperazine-1-carboxamid,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(piperidine-1-ylcarbonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(morpholine-4-ylcarbonyl)piperidine-4-amine,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-methyl-1N-phenylpiperidine-1-carboxamide, N-benzyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-methylpiperidin-1-carboxamid,
ethyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxylate,
methyl-4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-carboxylate,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2S)-piperidine-2-ylcarbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(2R)-piperidine-2-ylcarbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-pyridin-2-reparacin-4-amine,
methyl-N-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)cyclohexyl]glycinate,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2,2-dottorati)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(6-methylpyridazin-3-yl)piperidine-4-amine,
methyl-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)piperidine-1-yl]acetate,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)is piperidin-1-yl]-2-oxoethyl}-1-pyrimidine-2-reparacin-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-cyclopropylidene-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-{[(2S)-4,4-deformability-2-yl]carbonyl}piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(4,4-(debtor-L-prolyl)piperidine-4-amine,
1-(1H-benzimidazole-2-yl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl} piperidine-4-amine,
1-(2,1-benzisoxazol-3-ylcarbonyl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl} piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl)-1-(2,2,2-triptorelin)piperidine-4-amine,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(4-methoxyphenyl)piperidine-1-carboxamide,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(4-forfinal)piperidine-1-carboxamide,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(2,4-differenl)piperidine-1-carboxamide,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(3,4-differenl)piperidine-1-carboxamide,
4-({(1R)-1-(Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(2-forfinal)piperidine-1-carboxamide,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-(2-methoxyphenyl)piperidine-1-carboxamide,
4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-N-[4-(dimethylamino)phenyl]piperidine-1-carboxamide,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(5-fluoro-1H-indol-2-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(pyrazin-2-ylcarbonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(isoxazol-5-ylcarbonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(quinoline-2-ylcarbonyl)piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(3-methylpyridin-2-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(1H-1,2,4-triazole-3-ylcarbonyl)piperidine-4-amine,
1-(1,3-benzothiazol-2-ylcarbonyl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(6-methylpyridin-2-yl)carbonyl]PIP who ridin-4-amine,
1-(1-benzofuran-2-ylcarbonyl)-N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(6-herperidin-2-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-(2,4-differentail)piperidine-4-amine.

28. Compounds with the following names:
1-[4-({(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}amino)-piperidine-1-yl]butane-2-it,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(5-phenyl-1,3-oxazol-4-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(1-phenyl-1H-pyrazole-5-yl)carbonyl]piperidine-4-amine,
N-{(1R)-1-(4-Chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazole-1-ylmethyl)piperidine-1-yl]-2-oxoethyl}-1-[(6-vinylpyridin-2-yl)carbonyl]piperidine-4-amine.

29. A drug intended for the treatment or prevention of obesity, diabetes and sexual dysfunction, which can be affected by both sexes, for the treatment of cardiovascular diseases, for use in anti-inflammatory treatment or in the treatment of alcohol dependence, characterized in that it comprises connection is ormula (I) according to any one of claims 1 to 28 or additive salt of this compound with a pharmaceutically acceptable acid, or a hydrate or MES the compounds of formula (I).

30. Pharmaceutical composition for treatment or prevention of obesity, diabetes and sexual dysfunction, which can be affected by both sexes, for the treatment of cardiovascular diseases, for use in anti-inflammatory treatment or in the treatment of alcohol dependence, characterized in that it contains a compound of the formula (I) according to any one of claims 1 to 28 or a pharmaceutically acceptable salt, or a hydrate or MES this connection, and at least one pharmaceutically acceptable excipient.

31. The use of the compounds of formula (I) according to any one of claims 1 to 28 for obtaining a medicinal product intended for the treatment or prevention of obesity, diabetes and sexual dysfunction, which can be affected by both sexes, for the treatment of cardiovascular diseases, for use in anti-inflammatory treatment or in the treatment of alcohol dependence.

32. Use p, characterized in that the said sexual dysfunction are erectile dysfunction.

33. The method of obtaining the compounds of formula (I) according to any one of claims 1 to 21, characterized in that exercise rehabilitation amination of the compounds of formula (V):

in the presence of a derivative group, R4ketone type, and R1, R , R3, R4, R5,
Ra, Ra', Rb, Rb'and n have the meanings specified in any of paragraphs. 1-21.

34. Compounds of formulas (IV) and (V):

in which R1, Ra, Ra', Rb, Rb'have the values listed in any one of claims 1 to 21, Pg denotes a protective group, and:
n = 1, Raand Ra'identical or different, denote a hydrogen atom or an alkyl or cycloalkyl group, and Rband Rb'form together with the carbon atoms of the cycle to which they are attached, carbon bridge, containing 4-5 links.

35. Compounds of formula (VI), (XXVIII) and (XXIX), in which R1, R2, R3, R4R5, Ra, Ra', Rb, Rb'and n have the values listed in any one of claims 1 to 21, and in which R4denotes a group of formula (a) or (b)as described in any one of claims 1 to 21, and Pg denotes a protective group of the amine or hydroxyl:

36. The compounds of formula (II):

in which R1, Ra, Ra', Rband Rb'have the values listed in any one of claims 1 to 21, and Pg denotes a protective group, and
n=1, Raand Ra'identical or different, denote a hydrogen atom or an alkyl or cyclea kilou group, and Rband Rb'form together with the carbon atoms of the cycle to which they are attached, carbon bridge, containing 4-5 links.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: described is a new uniformly tritium-labeled 4,4-fluoro-N-{(1S)-3-[3-(3-isopropyl-5-methyl-4H-1,2,4-trizol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}cyclohexane carboiimide (maraviroc) of formula I .

EFFECT: said compound can be used in analysis of physiologically active compound-analogue.

1 cl, 1 ex, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I), their optically active stereoisomers, as well as to pharmaceutically acceptable salts possessing properties of ORL1 and µ-opiate receptors. In general formula , R1 represents H, alkyl(1-6C), []m represents-(CH2)m-, in which m equals 0 or 1, R2 represents halogen, CF3, alkyl(1-6C), phenyl, cyano, cyanoalkyl(1-3C), hydroxy, (1-3C)alkoxy, OCF3, acyl(2-7C), trifluoroacetyl, (1-3C)alkylsulfonyl or trifluoromethylsulfonyl, and n represents integer number 0-4 on condition that when n equals 2, 3 or 4, R2 substituents can be similar or different, A represents saturated ring, []0 and []p represents -(CH2)o and -(CH2)p, and o and p independently correspond to 0, 1 or 2, R3, R4, R5 and R6 independently represent hydrogen, alkyl(1-3C), or (R4 and R6) together can form alkylene bridge, containing 1-3 carbon atoms on condition that when o equals 2, R3 represents hydrogen, and when p equals 2, R5 represents hydrogen, R7 represents H, halogen, alkyl(1-6C). Invention also relates to pharmaceutical composition, intermediate compounds for obtaining formula (1) compounds.

EFFECT: compounds can be used for preparing medication for treating disorders and diseases such as alimentary behaviour disturbances, arterial hypertension.

8 cl, 3 dwg, 1 tbl, 45 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: method involves production of N-substituted 3β-aminonortropanes of formula I or one of acid-additive salts , where R1 represents optionally substituted residue chosen from group, including C1-C8alkyl, C2-C8alkenyl, C3-C8cycloalkyl and C6-C10aryl-C1-C8alkyl, characterised that either a) related 3-oxonortropane of formula IIA reacts with arylmethylamine of formula IIIA H2N-CH2-Ar (IIIA) where Ar stands for optionally substituted phenyl residue or optionally substituted 5 or 6-merous heteroaromatic residue with at least one heteroatom chosen from group including N, O and S, or b) related 3α-aminonortropane of formula IIB reacts with arylaldehyde of formula IIIB O-CH-Ar (IIIB). Produced in each case imine of formula IVA or IVB is transformed to thermodynamically stable tautomer, respectively isomer of formula V , then hydrolysed and if required transformed to related acid-additive salt.

EFFECT: produced compounds of formula I are valuable intermediate in chemical synthesis of various pharmaceutical reactants or represent pharmaceutical reactant, first of all as NMDA-receptor modulators; method allows for high-yield commercial production of high-purity 3-aminonortropanes.

9 cl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to a compound with general formula where R' stands for phenyl, unsubstituted or substituted with one or more substitutes, chosen from a group comprising alkyl, alkoxy group, halogen, -(CH2)oOH, -C(O)H, CF3, CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR'R", -NR'R"; R2 and R3 independently stand for hydrogen, halogen, alkyl, alkoxy group, OCHF2, OCH2F, OCF3 or CF3 and R4 and R5 independently stand for hydrogen, -(CH2)2SCH3, -(CH2)2S(O)2CH3, -(CH2)2S(O)2NHCH3, -(CH2)2NH2, -(CH2)2NHS(O)2CH3 or -(CH2)2NHC(O)CH3, R' stands for hydrogen, alkyl, -(CH2)oOH, -S(O)2- alkyl, -S(O)-alkyl, -S-alkyl; R" stands for hydrogen or alkyl; o stands for 0, 1, 2 or 3. The invention also relates to use of formula I compounds in making medicinal preparations for treating schizophrenia, for treating positive and negative symptoms of schizophrenia and medicine for treating schizophrenia.

EFFECT: obtaining new compounds with useful biological properties.

55 cl, 421 ex, 1 tbl

The invention relates to new cyclic amine derivatives of General formula I, where R1represents a phenyl group substituted by halogen atom,2represents C1- C8aliphatic acyl group or (C1- C4alkoxy)carbonyl group, R3represents a 3 - to 7-membered saturated cyclic amino group which may form a condensed ring, where the specified cyclic amino group substituted by the Deputy selected from the group comprising: mercaptopropyl, which can be unprotected or protected by a group selected from a number of protective groups, C1- C4alkyl group, substituted mercaptopropyl, which can be unprotected or protected by a group selected from a number of protective groups, and the number of protective groups for the specified mercaptopropyl includes C1- C20alcoholnye group, C3- C20alkenone group and benzoline group, and the said cyclic amino group, furthermore preferably a substituted group of the formula =CR4R5where R4represents a hydrogen atom, and R5represents a hydrogen atom, a C1- C4alkyl group, carboxypropyl, (C1- C4-alkoxy)carbonyl GRU

The invention relates to therapeutic active usacycling or azabicyclic compounds, method of their preparation and to pharmaceutical compositions comprising these compounds

The invention relates to derivatives of 3-(piperidinyl-1)-chroman-5,7-diol and 1-(4-hydroxyphenyl)-2-(piperidinyl-1)alkanol General formula I or their pharmaceutically acceptable salts accession acid, in which (a) R2and R5taken individually and R1, R2, R3and R4independently represent hydrogen, (C1-C6)-alkyl, halogen, HE or or7and R5represents methyl; or (b) R2and R5taken together form a ring chroman-4-ol, a R1, R3and R4each independently represent hydrogen, (C1-C6)-alkyl, halogen, HE or or7; R7represents methyl; and R6represents a substituted piperidinyl or 8-azabicyclo[3,2,1]octenidine derived; provided that (a) if R2and R5taken separately, at least one of R1, R2, R3and R4is not hydrogen; and (b) if R2and R5taken together, at least one of R1, R3and R4is not hydrogen, with the property that the NMDA antagonist

FIELD: organic chemistry, medicine, oncology.

SUBSTANCE: invention relates to derivatives of camptothecin of the general formula (I): wherein R1 represents alkyl or their pharmaceutically acceptable salts. Compounds of the formula (I) are intermediate compounds used in synthesis of camptothecin derivatives that possess anticancer activity.

EFFECT: valuable medicinal properties of compounds.

8 cl, 2 ex

FIELD: medicine.

SUBSTANCE: invention is related to new heterocyclic compounds of common formula (I), and also their pharmaceutically acceptable salts, hydrates and/or solvates, possessing properties of human neutrophil elastase. In common formula (I) , A means phenyl or pyridyl cycle, R1 and R3 each means atom of hydrogen, R2 means atom of fluorine, chlorine, bromine, nitro group or cyano group, R4 means cyano group, alkyl carbonyl group with number of carbon atoms in alkyl residue from one to four, or alkoxycarbonyl group with number of carbon atoms in alkoxyl residue from one to four, besides alkoxycarbonyk group with number of carbon items in alkoxyl residue from one to four, may be substituted with substituent, which is selected from the group that includes hydroxyl group, alkoxygroup with number of carbon atoms from one to four, alkoxycarbonyl group with number of carbon atoms in alkoxyl residue from one to four, mono- or dialkylaminogroup, with number of carbon atoms in each of alkyl residues from one to four, 5-6-member heteroaryl group, which contains from 1 to 4 heteroatoms in heteroaryl ring, selected from nitrogen, oxygen or sulfur, possibly susbstituted with alkyl group, which contains from 1 to 4 atoms of carbon and possibly condensed with benzene ring, and 5-8 member heterocyclyl group, which contains from 1 to 3 heteroatoms from group of nitrogen, oxygen or sulfur, or SO, SO2 possibly substituted with ketogroup, R5 means methyl group, R6 means atom of hydrogen, alkyl group with number of carbon atoms from one to four, mono- or dialkylaminocarbonyl group with number of carbon atoms in each of alkyl residues from one to four, etc., Y1, Y2, Y3, Y4 and Y5 each means CH-group. Invention is also related to pharmaceutical composition.

EFFECT: possibility of application for treatment of chronic obstructive lung diseases, acute coronary syndrome, acute myocardial infarction and progressing cardiac decompensation.

8 cl, 1 dwg, 111 ex

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula: I where R1 represents hydrogen or C1-7-alkyl; R2 and R3 independently represent hydrogen; R4 and R5 independently represent hydrogen; R6, R7, R8 and R9 independently represent hydrogen, C1-7-alkyl; and one of R6, R7 and R8 represents where R10 represents hydrogen, C1-7-alkyl; R11 represents hydrogen, C1-7-alkyl; one of R12 or R13 represents hydrogen, C1-7-alkyl or fluorine-C1-7-alkyl; and the other represents undivided electron pair; R14 represents hydrogen, C1-7-alkyl, halogen; R15 represents aryl or aryl substituted with 1-3 groups chosen from C1-7-alkyl C1-7-alkoxy, halogen, fluorine-C1-7-alkyl and fluorine-C1-7-alkoxy; and n has a value 1, 2 or 3; and to all their enantiomers and to pharmaceutically acceptable salts and/or esters. The invention also concerns the pharmaceutical compositions.

EFFECT: production of new biologically active compounds with agonist activity with respect to PPARδ and PPARα.

20 cl, 25 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: carboxylic acid compounds are presented by formula (I) where R1 represents (1) hydrogen atom, (2) C1-4alkyl; E represents -CO-; R2 represents (1) halogen atom, (2) C1-6 alkyl, (3) trihalogen methyl; R3 represents (1) halogen atom, (2) C1-6alkyl; R4 represents (1) hydrogen atom; R5 represents (1) C1-6alkyl; represents phenyl; G represents (1) C1-6alkylene; represents 9-12-merous bicyclic heterocycle containing heteroatoms, chosen of 1-4 nitrogen atoms, one or two oxygen atoms; m represents 0 or an integer 1 to 4, n represents 0 or an integer 1 to 4, and i represents 0 or an integer 1 to 11 where R2 can be identical or different provided m is equal to 2 or more, R3 can be identical or different provided n is equal to 2 or more, and R5 can be identical or different provided i is equal to 2 or more; both R12 and R13, independently represent (1) C1-4alkyl, (2) halogen atom, (3) hydroxyl or (4) hydrogen atom, or R12 and R13 together represent (1) oxo or (2) C2-5alkylene and where provided R12 and R13 simultaneously represent hydrogen atom, carboxylic acid compound presented by formula (I), represents a compound chosen from the group including the compounds (1) - (32), listed in cl.1 of the patent claim. Besides the invention concerns a pharmaceutical composition based in the compound of formula I and to application of the compound of formula I for making the pharmaceutical composition.

EFFECT: there are produced new carboxylic acid derivatives with antagonistic activity with respect to DP receptor.

14 cl, 74 ex

Amide derivatives // 2375352

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula I, to its pharmaceutically acceptable salts exhibiting properties of inhibitors of cytokine production, such as TNF (tumour necrosis factor) and various members of interleukins (IL) family, and properties of kinase inhibitors, particularly p38α kinase. The invention also concerns methods for producing; pharmaceutical compositions and application thereof for making the medicines for treating diseases affected by the compound of the invention with specified activity. In formula I , m represents 0, 1 or 2; R1 represents halogeno, hydroxy, (1-6C) alkyl, (1-6C)alkoxy, (2-6C)alkenyl, (2-6C) alkinyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, amino-(2-6C) alkoxy, (1-6C)alkylamino-(2-6C)alkoxy, di-[(1-6C)alkyl]amino-(2-6C)alkoxy, N-(1-6C)alkylcarbamoyl - (1-6C)alkoxy, di[(1-6C) alkyl]amino-(1-6C)alkyl, hydroxy-(2-6C)alkylamino, heteroaryl-(1-6C)alkoxy, heterocyclyl, heterocyclyloxy and heterocyclyl-(1-6C)alkoxy and wherein any heteroaryl or heterocyclyl group in substitute representing R1, can probably have 1 or 2 substitutes chosen from hydroxy, halogeno, (1-6C) alkyl, (2-6C)alkinyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-6C)alkyl, (1-6C)alkoxycarbonyl, (2-6C) alkanoyl, halogen-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, carboxy- (1-6C)alkyl and methylsulphonyl and wherein any said substitute representing R1 which contains group CH2 attached to 2 carbon atoms, or group CH3 attached to carbon or nitrogen atom, can probably have with each specified group CH2 or CH3, one or two substitutes chosen from halogeno, hydroxy, amino, triflouromethyl, oxo, carboxy, acetamido, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkyamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, halogen-(1-6C)alkyl, (1-6C)alkoxycarbonyl, carbamoyl, N, N-di-[(1-6)alkyl]carbamoyl, (1-6C)alkylsulphonyl, heteroaryl, heteroaryl-(1-6)alkyl and heterocyclyloxy and wherein any heterocyclyl group in substitute representing R1, can probably have 1 oxo-subsitute; R2 represents trifluoromethyl or (1-6C)alkyl; R3 represents hydrogen or (1-6C)alkyl; and R4 represents (3-6C)cycloalkyl, and R4 can be optionally substituted with one or more substitutes chosen from (1-6C)alkyl; and wherein heteroaryl represents aromatic 5- or 6-merous monocyclic ring containing one or two heteroatoms chosen from oxygen, nitrogen and sulphur; heterocyclyl represents saturated 3-10-merous monocyclic or bicyclic ring, each containing one or two heteroatoms chosen from oxygen, nitrogen and sulphur.

EFFECT: improved efficiency.

24 cl, 16 tbl, 66 ex

Amide derivatives // 2375352

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula I, to its pharmaceutically acceptable salts exhibiting properties of inhibitors of cytokine production, such as TNF (tumour necrosis factor) and various members of interleukins (IL) family, and properties of kinase inhibitors, particularly p38α kinase. The invention also concerns methods for producing; pharmaceutical compositions and application thereof for making the medicines for treating diseases affected by the compound of the invention with specified activity. In formula I , m represents 0, 1 or 2; R1 represents halogeno, hydroxy, (1-6C) alkyl, (1-6C)alkoxy, (2-6C)alkenyl, (2-6C) alkinyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, amino-(2-6C) alkoxy, (1-6C)alkylamino-(2-6C)alkoxy, di-[(1-6C)alkyl]amino-(2-6C)alkoxy, N-(1-6C)alkylcarbamoyl - (1-6C)alkoxy, di[(1-6C) alkyl]amino-(1-6C)alkyl, hydroxy-(2-6C)alkylamino, heteroaryl-(1-6C)alkoxy, heterocyclyl, heterocyclyloxy and heterocyclyl-(1-6C)alkoxy and wherein any heteroaryl or heterocyclyl group in substitute representing R1, can probably have 1 or 2 substitutes chosen from hydroxy, halogeno, (1-6C) alkyl, (2-6C)alkinyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-6C)alkyl, (1-6C)alkoxycarbonyl, (2-6C) alkanoyl, halogen-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, carboxy- (1-6C)alkyl and methylsulphonyl and wherein any said substitute representing R1 which contains group CH2 attached to 2 carbon atoms, or group CH3 attached to carbon or nitrogen atom, can probably have with each specified group CH2 or CH3, one or two substitutes chosen from halogeno, hydroxy, amino, triflouromethyl, oxo, carboxy, acetamido, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkyamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, halogen-(1-6C)alkyl, (1-6C)alkoxycarbonyl, carbamoyl, N, N-di-[(1-6)alkyl]carbamoyl, (1-6C)alkylsulphonyl, heteroaryl, heteroaryl-(1-6)alkyl and heterocyclyloxy and wherein any heterocyclyl group in substitute representing R1, can probably have 1 oxo-subsitute; R2 represents trifluoromethyl or (1-6C)alkyl; R3 represents hydrogen or (1-6C)alkyl; and R4 represents (3-6C)cycloalkyl, and R4 can be optionally substituted with one or more substitutes chosen from (1-6C)alkyl; and wherein heteroaryl represents aromatic 5- or 6-merous monocyclic ring containing one or two heteroatoms chosen from oxygen, nitrogen and sulphur; heterocyclyl represents saturated 3-10-merous monocyclic or bicyclic ring, each containing one or two heteroatoms chosen from oxygen, nitrogen and sulphur.

EFFECT: improved efficiency.

24 cl, 16 tbl, 66 ex

FIELD: medicine.

SUBSTANCE: compounds can be used for treatment and prevention of diseases associated with activity of specified enzyme, such as diabetes, obesity, diseases associated with food intake, dyslipidemia and hypertension. In general formula (I) , R1 represents methyl, ethyl, cyclopropyl, cyclobutyl, isopropyl, tert-butyl, methoxymethyl, cyclopropyl methoxymethyl, 2-methyl thiazolyl, morpholinyl methyl or phenyl; R2 represents hydrogen, C1-4alkyl or phenyl; R3 represents hydrogen, C1-4alkyl or phenyl; R4 represents phenyl, naphthyl, thiophenyl, quinolyl or piperidyl where phenyl, naphthyl, thiophenyl, quinolyl and piperidyl are optionally substituted with one to three substitutes independently chosen of C1-4alkyl, halogen, C1-4alkoxy, cyano, trifluoromethyl, phenyl, phenyls C1-4alkyl, phenyloxy, oxasolyl and pyridinyl; R5 represents hydrogen, C1-4alkyl, phenyl-C1-4alkyl, C3-6dicloalkyl-C1-4alkyl or aminocarbonylC1-4alkyl.

EFFECT: higher clinical effectiveness.

17 cl, 2 dwg, 72 ex

FIELD: medicine.

SUBSTANCE: there are described 2-(R)-phenylpropionic acid derivatives of formula (1) and their pharmaceutically acceptable salts where R' is chosen from H, OH and provided R' represents H, R is chosen from H, C1-C5-alkyl, C3-C6-cycloalkyl, C1-C3-alkoxy, thiazolyl, substituted CF3, the remained formula -CH2-CH2-Z-(CH2- CH2O)nR', where n is equal to 2, and Z represents oxygen, the remained formula - (CH2)n-NRaRb, the remained formula SO2Rd, provided R' represents OH, R is chosen from C1-C5alkyl. The compounds are applied to inhibit chemotactic activation of neutrophils (PMN leukocytes) induced by interaction of interleukine-8 (IL-8) and membrane receptors CXCR1 and CXCR2. The compounds are applied to prevent and treat the pathologies generated by specified activation. There are also described application of the compounds for manufacturing of medicinal agents for treating psoriasis, nonspecific ulcerative colitis, melanoma, angiogenesis, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and to prevent and treat the damages caused by ischemia and reperfusion, the pharmaceutical composition and method for making the compounds of formula (1) where R' represents H and R - group SO2Rd.

EFFECT: higher clinical effectiveness.

8 cl, 3 tbl, 11 ex

FIELD: medicine.

SUBSTANCE: invention relates to amidines of formula (I) and to their derivatives, methods for making thereof and pharmaceutical compositions containing amidines of formula (I). According to said invention, amidines are applicable for inhibition of IL-8 induced chemotactic factor, and can be applied to produce medicine agents for treating psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and for preventing and treating injuries caused by ischemia and reperfusion.

EFFECT: higher clinical effectiveness.

7 cl, 6 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicinal products and concerns application of alpha adrenoceptor antagonist as a preparation for treating ischemic diseases of spinal marrow and associated ischemic diseases of other organs prescribed in an effective dose.

EFFECT: invention allows extending range of medicinal agents for treating conditions associated with spinal marrow ischemia in blood circulation disturbance.

8 cl, 3 ex

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